Scientists are one step closer to mimicking the way biological systems interact and process information in the body -- a vital step toward developing new forms of biorobotics and novel treatment approaches for several muscle-related health problems such as muscular degenerative disorders, arrhythmia and limb loss.

Using cardiac muscle cells and cardiac fibroblasts -- cells found in connective heart tissue -- researchers at the University of Notre Dame have created a "living diode," which can be used for cell-based information processing, according to a recent study in Advanced Biosystems. Bioengineers created the muscle-based circuitry through a novel, self-forming, micro patterning approach.

Using muscle cells opens the door to functional, biological structures or "computational tissues" that would allow an organ to control and direct mechanical devices in the body. The design arranges the two types of cells in a rectangular pattern, separating excitable cells from nonexcitable cells, allowing the team to transduce electrical signals unidirectionally and achieve a diode function using living cells. In addition to the diode-like function, the natural pacing ability of the muscle cells allowed Pinar Zorlutuna, assistant professor of aerospace and mechanical engineering, and her team to pass along information embedded in the electrical signals by modulating the frequency of the cells' electrical activity. Zorlutuna's research was funded by the National Science Foundation.

"Muscle cells have the unique ability to respond to external signals while being connected to fibroblasts internally through intercellular junctions. By combining these two cell types, we have the ability to initiate, amplify and propagate signals directionally," said Zorlutuna, who is also director of the Tissue Engineering Laboratory at the university. "The success of these muscle-cell diodes offers a path toward linking such cell-based circuitry to a living system -- and creating functional control units for biomedical engineering applications such as bioactuators or biosensors."

The team's work presents a new option in biocomputing, which has focused primarily on using gene circuitries of genetically modified single-cells or neuronal networks doped with chemical additives to create information processing systems. The single-cell options are slower to process information since they relay on chemical processes, and neuronal-based approaches can misfire signals, firing backward up to 10 percent of the time.

Zorlutuna explores biomimetic environments in order to understand and control cell behavior. She also studies cell-cell and cell-environment interactions through tissue and genetic engineering, and micro- and nanotechnology at the Notre Dame Center for Nano Science and Technology. She is a researcher at the University's Center for Stem Cells and Regenerative Medicine and the Harper Cancer Research Institute.

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Myocardial Stem Cell Patch Developed with 3D Printer BusinessKorea The myocardial patch, which is printed with a 3D printer and attached to the hearts of such patients for blood vessel and tissue regeneration, has a structure in which cardiac extracellular matrices are used as bio ink and cardiac stem cells and ...

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When Becky's baby girl started sweating, vomiting and struggling to breathe while breastfeeding , she knew something was wrong.

But despite taking her daughter, Kirsty, to the GP numerous times, she was dismissed as "neurotic" and "unable to cope", a new book reveals.

Even when the six-month-old was finally referred to hospital for X-Rays, paediatricians wrongly diagnosed her condition as bronchitis.

It was only when she was close to death, lying limp and grey in her terrified mum's arms, that the true cause of her illness was diagnosed.

She had severe heart failure after "multiple heart attacks" - which she had suffered from 'silently', unable to communicate or understand them.

Kirsty wasnt gaining weight," writes world-famous cardiac surgeon Stephen Westaby in his remarkable book, Fragile Lives , published today.

"She had a pasty, washed-out look and a cough like a dogs bark.

In reality, this baby was suffering repeated small heart attacks with excruciating chest pain that she could neither communicate nor understand.

"The human body can be outlandishly cruel.

Stephen, from Oxford, operated on Kirsty following her ALCAPA (anomalous left coronary artery from the pulmonary artery) diagnosis.

He found the situation "even worse" than he had thought and, at one point, Becky and her husband were warned they would likely lose their baby.

However, in a desperate, last-ditch attempt to save the youngster's life, Stephen carried out a procedure that had never been done before in a child.

He made her heart smaller by removing almost a third of it, before stitching the organ back up until it looked like a "quivering black banana".

Amazingly, he saved his tiny patient's life.

Today, Kirsty is an 18-year-old, athletic student. She has been able to attend school, go to prom and spend time with her friends.

Her incredible story is one of many featured in Stephen's new book, which details some of the surgeon's most extraordinary and poignant cases.

Others include a woman who lived the horror of locked-in syndrome, and a man whose life was powered by a battery for more than seven years

They all include drama, emotion and blood (lots of it).

Having grown up on a council estate in Scunthorpe, North Lincolnshire, Stephen went into cardiac surgery after watching his granddad die of heart failure.

He tells Mirror Online that, despite his passion for the speciality and his determination, he "never anticipated" he would even get to medical school.

But over the past nearly 40 years, he has become an acclaimed heart surgeon and pioneer, responsible for a number of significant developments in the field.

He invented a T-Y stent - dubbed the "Westaby" tube - to bypass damaged airways, and became the first surgeon to fit a patient with a new type of artificial heart.

The patient, Peter, died aged 69 after over seven years of "extra life". "He was the first to reveal the true potential of blood pump technology," writes Stephen in his book.

The surgeon, who has worked in hospitals in the UK and abroad, says he learned "very early on" that a lot of patients were being turned away for heart transplants.

"Although transplants were great for patients, a lot of others were being turned away," he says. "Very few people can have heart transplants.

"They need someone else to die to get their heart.

He says that, even as a trainee, he was interested in alternative options for the unfortunate patients who could not receive a transplant.

In his book, he describes how, as a student, he was called to assist an operation on a young car crash victim after drinking pints in the pub.

"Bad problem, both the injury and the beer," he writes in his book.

"Not so much the amount of alcohol - we were used to that - more the volume of urine to pass during a four-hour operation."

To get through the surgery without losing concentration or having to leave, he reveals how he used rubber tubing so his urine would run into his surgical boots.

He admits, at one point, he had to cough loudly to disguise the "squelching sound".

When you start doing any surgery, it is scary. It takes you a few months to get into," says the dad-of-two. "Its very taxing."

In subsequent decades, Stephen went on to save hundreds of lives, repeatedly taking chances and pushing the boundaries of heart surgery.

This was all part of being a pioneer, pushing the profession to its limit," he says.

Far from working nine-to-five, the surgeon spent his mornings, afternoons and evenings dedicated to his "day job".

To become a heart surgeon I believe you have to work continuously in the way I did in the old days," he tells Mirror Online.

"We had ward rounds at 5am, then wed operate at 7am.

Stephen would spend the rest of the day operating on patients, before going to the research lab. In the evenings, he'd return to intensive care.

"It needs that sort of dedication," he says.

Indeed, it was this dedication that saw him cut a conference in Australia short to rush back to perform life-saving surgery on Kirsty.

Stephen had been in the country for just 13 hours when he received a call from Nick Archer, his paediatric cardiology colleague at Oxfords John Radcliffe Hospital.

No one calls with good news at night, he notes in his book.

And he was right.

He was told that there was a sick baby with ALCAPA - a rare but serious cardiac anomaly - who desperately needed his help.

He later discovered that Kirsty - in whom fate had installed a lethal self-destruct mechanism" - had shown signs of distress within days of her birth.

Her mum Becky, who already had a three-year-old son, noticed beads of sweat were trickling from her baby's nose whenever she tried to breastfeed her.

However, a paediatrician dismissed the infant's symptoms, Stephen writes in his book, deeming the move an example of "p***-poor medicine".

Within a matter of weeks, Kirsty was sweating, vomiting and struggling to breathe during feeds. However, she had no temperature.

Her concerned mum repeatedly took her to visit the doctor, but was "deemed neurotic and unable to cope", according to Fragile Lives.

At the time, Becky's husband was working abroad, away from their daughter who had a "pasty look" and a "cough like a dog's bark".

After eventually managing to get Kirsty referred to a hospital for X-Rays, Becky was told that her baby was suffering from bronchitis.

Feeling desperate and certain that something "dreadful" was going to happen, she later took the "grey" youngster to another hospital.

But there, she was diagnosed with the same condition.

Now late at night, Becky demanded a further X-Ray. Shockingly, she was "told off for her unreasonable attitude," Stephen writes in his moving book.

However, after the scan, the mum finally had her fears confirmed.

Her daughter was found to have a massive heart, with medics having reportedly misinterpreted heart shadows on her X-Rays as fluid.

Kirsty was rushed to Oxford's specialist childrens heart unit. By then, she was very cold and suffering from severe heart failure, Stephen says.

While flying back from Australia, the surgeon devised an alternative technique for the operation in a bid to increase the baby's chance of survival.

After landing in the UK, however, he was shocked by Kirsty's condition.

"She was emaciated, with virtually no body fat, her heaving ribs and rapid breathing a consequence of her congested lungs, and her abdomen swollen with fluid," he writes.

He adds: Without immediate surgery, shed be dead within days.

Joined by his surgical team, Stephen opened up the baby's small body with a scalpel blade, an electrical saw and a rib retractor while her parents faced an anxious wait.

He describes in his book how he found her heart to be the size of a lemon.

Babies' hearts are typically the size of a walnut.

Stephen then goes on to explain how he replumbed Kirsty's heart's blood supply and removed up to 30 per cent of her organ in an attempt to save her.

Incredibly, the surgery was a success.

The operation "provided some of the first evidence that an infants own cardiac stem cells can regenerate heart muscle and actually remove fibrous tissue," Stephen says.

"Adult hearts cannot recover in the same way," he writes.

Speaking to the Mirror Online, the surgeon describes how he "always put the patient first", even if it meant the possibility of being sacked.

He admits he did things "off piste" and, when he didn't have the money to perform certain procedures, he would raise charitable funds.

I used to operate on everyone from premature babies in their cots to people all the way through to their nineties," he says.

"Every one is precious."

He adds that it takes a "special sort of person" - one who is extremely skilled, gutsy and empathetic - to operate on babies and children.

"I think you find it difficult every time you lose a patient, no matter how high risk they are," he says.

"I used to really hate having to go out of an operating theatre and telling [relatives] their loved one had died.

Stephen, who describes his own story as one of "grim determination", worked on around 12,000 patients during his career.

He estimates between 300 and 400 died earlier than they would have.

I did lose an awful lot of patients," he says.

"There are lots of cases that have stuck with me.

But he adds: "Very few heart patients die because the surgeon doesnt do a good job.

He says some patients suffer complications which aren't managed well, while the quality of the intensive care team can also have an impact.

Nowadays, surgeons' death rates are published. There is also a risk of legal action by grief-stricken and angry relatives, Stephen says.

This 'naming and shaming' culture, he claims, is having a negative effect on the profession and putting graduates off from going into heart surgery.

"It's a worrying time for trainees," he says, describing how there are "serious weaknesses" with the system. "Surgeons now have their death rates published."

He adds that this also means it's difficult to maintain consistent intensive care teams.

"There's a lot of agency nurses, people not familiar with protocol," he says.

Stephen, who established the Oxford Heart Centre in the 1980s, recently retired from surgery after developing Dupuytren's contracture, or a 'claw hand'.

"My hand was warped into the position in which I held the scissors, the needle holder, the sternal saw," the 68-year-old writes in his book.

Now, he is working in two "very exciting" roles, one of which involves a proposed Wellness and Life Science Village in Llanelli, Wales.

He is also medical director at the regenerative medicine firm, Celixir , which he says has made "very important" developments for people with heart failure.

Reflecting on his incredible career, Stephen, who lives with his wife, Sarah, 63, acknowledges that he "didn't give enough time" to his family.

He met his spouse - a "free spirit from Africa" - over an open chest in Accident & Emergency, where she was working as a sister.

Stephen has a 38-year-old daughter - by his first wife, Jane - and a 28-year-old son - by Sarah, as well as two young granddaughters.

I never gave enough time to my kids and my grandchildren," he admits.

But he adds that one of the reasons he wrote his book, "was so they could see why I wasnt with them as much as I could be".

Stephen appeared on ITV's This Morning today, along with Kirsty and Becky.

Viewers have since taken to social media to praise his "amazing" and "remarkable" work, with some calling for him to be knighted.

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A new revolutionary stem cell technique is being used to treat those suffering from damaged muscles without the cancer risk that was previously present. This was the first time that researchers had successfully implanted synthetic stem cardiac cells that managed to repair the muscle that a previous heart attack has weakened. Cancer was previously a risk with traditional stem cell therapy as scientists were unable to stop formertumors as the cells continued to replicate.

This procedure is mostly performed on those suffering from blood or bone marrow cancers such as leukemia. But, researchers are also working on developing effective stem cell treatments for those diagnosed with neurodegenerative diseases such as Parkinsons and heart disease too.

Synthetic stem cells are very handy because unlike natural stem cells, theyre easy to preserve and can be adapted to be used in various parts of the body. Ke Cheng, associate professor of molecular biomedical sciences at North Carolina State University, said, We are hoping that this may be the first step towards a truly off-the-shelf cell product that would enable people to receive beneficial stem cell therapies when theyre needed, without costly delays.

[The study can be found here.]

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:Pioneering Stem Cell Technique Promise Muscle Regeneration Without Cancer Risk

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Cardiac muscle cells or cardiomyocytes (also known as myocardiocytes[1] or cardiac myocytes[2]) are the muscle cells (myocytes) that make up the cardiac muscle. Each myocardial cell contains myofibrils, which are specialized organelles consisting of long chains of sarcomeres, the fundamental contractile units of muscle cells. Cardiomyocytes show striations similar to those on skeletal muscle cells. Unlike multinucleated skeletal cells, the majority of cardiomyocytes contain only one nucleus, although they may have as many as four.[3] Cardiomyocytes have a high mitochondrial density, which allows them to produce adenosine triphosphate (ATP) quickly, making them highly resistant to fatigue.

There are two types of cells within the heart: the cardiomyocytes and the cardiac pacemaker cells. Cardiomyocytes make up the atria (the chambers in which blood enters the heart) and the ventricles (the chambers where blood is collected and pumped out of the heart). These cells must be able to shorten and lengthen their fibers and the fibers must be flexible enough to stretch. These functions are critical to the proper form during the beating of the heart.[4]

Cardiac pacemaker cells carry the impulses that are responsible for the beating of the heart. They are distributed throughout the heart and are responsible for several functions. First, they are responsible for being able to spontaneously generate and send out electrical impulses. They also must be able to receive and respond to electrical impulses from the brain. Lastly, they must be able to transfer electrical impulses from cell to cell.[5]

All of these cells are connected by cellular bridges. Porous junctions called intercalated discs form junctions between the cells. They permit sodium, potassium and calcium to easily diffuse from cell to cell. This makes it easier for depolarization and repolarization in the myocardium. Because of these junctions and bridges the heart muscle is able to act as a single coordinated unit.[6][7]

The cardiomyocytes are about 100 to 150 micrometers long and 15 to 20 micrometers in diameter.[citation needed]

Humans are born with a set number of heart muscle cells, or cardiomyocytes, which increase in size as heart grows larger during childhood development. Recent evidence suggests that cardiomyocytes are actually slowly turned over as we age, but that less than 50% of the cardiomyocytes we are born with are replaced during a normal life span.[8] The growth of individual cardiomyocytes not only occurs during normal heart development, it also occurs in response to extensive exercise (athletic heart syndrome), heart disease, or heart muscle injury such as after a myocardial infarction. A healthy adult cardiomyocyte has a cylindrical shape that is approximately 100m long and 10-25m in diameter. Cardiomyocyte hypertrophy occurs through sarcomerogenesis, the creation of new sarcomere units in the cell. During heart volume overload, cardiomyocytes grow through eccentric hypertrophy.[9] The cardiomyocytes extend lengthwise but have the same diameter, resulting in ventricular dilation. During heart pressure overload, cardiomyocytes grow through concentric hypertrophy.[9] The cardiomyocytes grow larger in diameter but have the same length, resulting in heart wall thickening.

Cardiac action potential consists of two cycles, a rest phase and an active phase. These two phases are commonly understood as systole and diastole. The rest phase is considered polarized. The resting potential during this phase of the beat separates the ions such as sodium, potassium and calcium. Myocardial cells possess the property of automaticity or spontaneous depolarization. This is the direct result of a membrane which allows sodium ions to slowly enter the cell until the threshold is reached for depolarization. Calcium ions follow and extend the depolarization even further. Once calcium stops moving inward, potassium ions move out slowly to produce repolarization. The very slow repolarization of the CMC membrane is responsible for the long refractory period.[10][11]

Myocardial infarction, commonly known as a heart attack, occurs when the heart's supplementary blood vessels are obstructed by an unstable build-up of white blood cells, cholesterol, and fat. With no blood flow, the cells die, causing whole portions of cardiac tissue to die. Once these tissues are lost, they cannot be replaced, thus causing permanent damage. Current research indicates, however, that it may be possible to repair damaged cardiac tissue with stem cells,[12] as human embryonic stem cells can differentiate into cardiomyocytes under appropriate conditions.[13]

The cardiomyopathies are a group of diseases characterized by disruptions to cardiac muscle cell growth and / or organization. Presentation can range from asymptomatic to sudden cardiac death.

Cardiomyopathy can be caused by genetic, endocrine, environmental, or other factors.

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Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to an embryonic stem celllike state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells. Although these cells meet the defining criteria for pluripotent stem cells, it is not known if iPSCs and embryonic stem cells differ in clinically significant ways. Mouse iPSCs were first reported in 2006, and human iPSCs were first reported in late 2007. Mouse iPSCs demonstrate important characteristics of pluripotent stem cells, including expressing stem cell markers, forming tumors containing cells from all three germ layers, and being able to contribute to many different tissues when injected into mouse embryos at a very early stage in development. Human iPSCs also express stem cell markers and are capable of generating cells characteristic of all three germ layers.

Although additional research is needed, iPSCs are already useful tools for drug development and modeling of diseases, and scientists hope to use them in transplantation medicine. Viruses are currently used to introduce the reprogramming factors into adult cells, and this process must be carefully controlled and tested before the technique can lead to useful treatment for humans. In animal studies, the virus used to introduce the stem cell factors sometimes causes cancers. Researchers are currently investigating non-viral delivery strategies. In any case, this breakthrough discovery has created a powerful new way to "de-differentiate" cells whose developmental fates had been previously assumed to be determined. In addition, tissues derived from iPSCs will be a nearly identical match to the cell donor and thus probably avoid rejection by the immune system. The iPSC strategy creates pluripotent stem cells that, together with studies of other types of pluripotent stem cells, will help researchers learn how to reprogram cells to repair damaged tissues in the human body.

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Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor (multipotentiMSC, also called an induced multipotent progenitor celliMPC) or unipotent(iUSC) according to their developmental potential and degree of dedifferentiation. Progenitors are obtained by so-called direct reprogramming or directed differentiation and are also called induced somatic stem cells.

Three techniques are widely recognized:[1]

In 1895 Thomas Morgan removed one of a frog's two blastomeres and found that amphibians are able to form whole embryos from the remaining part. This meant that the cells can change their differentiation pathway. In 1924 Spemann and Mangold demonstrated the key importance of cellcell inductions during animal development.[20] The reversible transformation of cells of one differentiated cell type to another is called metaplasia.[21] This transition can be a part of the normal maturation process, or caused by an inducement.

One example is the transformation of iris cells to lens cells in the process of maturation and transformation of retinal pigment epithelium cells into the neural retina during regeneration in adult newt eyes. This process allows the body to replace cells not suitable to new conditions with more suitable new cells. In Drosophila imaginal discs, cells have to choose from a limited number of standard discrete differentiation states. The fact that transdetermination (change of the path of differentiation) often occurs for a group of cells rather than single cells shows that it is induced rather than part of maturation.[22]

The researchers were able to identify the minimal conditions and factors that would be sufficient for starting the cascade of molecular and cellular processes to instruct pluripotent cells to organize the embryo. They showed that opposing gradients of bone morphogenetic protein (BMP) and Nodal, two transforming growth factor family members that act as morphogens, are sufficient to induce molecular and cellular mechanisms required to organize, in vivo or in vitro, uncommitted cells of the zebrafish blastula animal pole into a well-developed embryo.[23]

Some types of mature, specialized adult cells can naturally revert to stem cells. For example, "chief" cells express the stem cell marker Troy. While they normally produce digestive fluids for the stomach, they can revert into stem cells to make temporary repairs to stomach injuries, such as a cut or damage from infection. Moreover, they can make this transition even in the absence of noticeable injuries and are capable of replenishing entire gastric units, in essence serving as quiescent "reserve" stem cells.[24] Differentiated airway epithelial cells can revert into stable and functional stem cells in vivo.[25]

After injury, mature terminally differentiated kidney cells dedifferentiate into more primordial versions of themselves and then differentiate into the cell types needing replacement in the damaged tissue[26] Macrophages can self-renew by local proliferation of mature differentiated cells.[27][28] In newts, muscle tissue is regenerated from specialized muscle cells that dedifferentiate and forget the type of cell they had been. This capacity to regenerate does not decline with age and may be linked to their ability to make new stem cells from muscle cells on demand.[29]

A variety of nontumorigenic stem cells display the ability to generate multiple cell types. For instance, multilineage-differentiating stress-enduring (Muse) cells are stress-tolerant adult human stem cells that can self-renew. They form characteristic cell clusters in suspension culture that express a set of genes associated with pluripotency and can differentiate into endodermal, ectodermal and mesodermal cells both in vitro and in vivo.[30][31][32][33][34]

Other well-documented examples of transdifferentiation and their significance in development and regeneration were described in detail.[35][36]

Induced totipotent cells can be obtained by reprogramming somatic cells with somatic-cell nuclear transfer (SCNT). The process involves sucking out the nucleus of a somatic (body) cell and injecting it into an oocyte that has had its nucleus removed[3][5][37][38]

Using an approach based on the protocol outlined by Tachibana et al.,[3] hESCs can be generated by SCNT using dermal fibroblasts nuclei from both a middle-aged 35-year-old male and an elderly, 75-year-old male, suggesting that age-associated changes are not necessarily an impediment to SCNT-based nuclear reprogramming of human cells.[39] Such reprogramming of somatic cells to a pluripotent state holds huge potentials for regenerative medicine. Unfortunately, the cells generated by this technology, potentially are not completely protected from the immune system of the patient (donor of nuclei), because they have the same mitochondrial DNA, as a donor of oocytes, instead of the patients mitochondrial DNA. This reduces their value as a source for autologous stem cell transplantation therapy, as for the present, it is not clear whether it can induce an immune response of the patient upon treatment.

Induced androgenetic haploid embryonic stem cells can be used instead of sperm for cloning. These cells, synchronized in M phase and injected into the oocyte can produce viable offspring.[40]

These developments, together with data on the possibility of unlimited oocytes from mitotically active reproductive stem cells,[41] offer the possibility of industrial production of transgenic farm animals. Repeated recloning of viable mice through a SCNT method that includes a histone deacetylase inhibitor, trichostatin, added to the cell culture medium,[42] show that it may be possible to reclone animals indefinitely with no visible accumulation of reprogramming or genomic errors[43] However, research into technologies to develop sperm and egg cells from stem cells raises bioethical issues.[44]

Such technologies may also have far-reaching clinical applications for overcoming cytoplasmic defects in human oocytes.[3][45] For example, the technology could prevent inherited mitochondrial disease from passing to future generations. Mitochondrial genetic material is passed from mother to child. Mutations can cause diabetes, deafness, eye disorders, gastrointestinal disorders, heart disease, dementia and other neurological diseases. The nucleus from one human egg has been transferred to another, including its mitochondria, creating a cell that could be regarded as having two mothers. The eggs were then fertilised and the resulting embryonic stem cells carried the swapped mitochondrial DNA.[46] As evidence that the technique is safe author of this method points to the existence of the healthy monkeys that are now more than four years old and are the product of mitochondrial transplants across different genetic backgrounds.[47]

In late-generation telomerase-deficient (Terc/) mice, SCNT-mediated reprogramming mitigates telomere dysfunction and mitochondrial defects to a greater extent than iPSC-based reprogramming.[48]

Other cloning and totipotent transformation achievements have been described.[49]

Recently some researchers succeeded to get the totipotent cells without the aid of SCNT. Totipotent cells were obtained using the epigenetic factors such as oocyte germinal isoform of histone.[50] Reprogramming in vivo, by transitory induction of the four factors Oct4, Sox2, Klf4 and c-Myc in mice, confers totipotency features. Intraperitoneal injection of such in vivo iPS cells generates embryo-like structures that express embryonic and extraembryonic (trophectodermal) markers.[51]

iPSc were first obtained in the form of transplantable teratocarcinoma induced by grafts taken from mouse embryos.[52] Teratocarcinoma formed from somatic cells.[53]Genetically mosaic mice were obtained from malignant teratocarcinoma cells, confirming the cells' pluripotency.[54][55][56] It turned out that teratocarcinoma cells are able to maintain a culture of pluripotent embryonic stem cell in an undifferentiated state, by supplying the culture medium with various factors.[57] In the 1980s, it became clear that transplanting pluripotent/embryonic stem cells into the body of adult mammals, usually leads to the formation of teratomas, which can then turn into a malignant tumor teratocarcinoma.[58] However, putting teratocarcinoma cells into the embryo at the blastocyst stage, caused them to become incorporated in the inner cell mass and often produced a normal chimeric (i.e. composed of cells from different organisms) animal.[59][60][61] This indicated that the cause of the teratoma is a dissonance - mutual miscommunication between young donor cells and surrounding adult cells (the recipient's so-called "niche").

In August 2006, Japanese researchers circumvented the need for an oocyte, as in SCNT. By reprograming mouse embryonic fibroblasts into pluripotent stem cells via the ectopic expression of four transcription factors, namely Oct4, Sox2, Klf4 and c-Myc, they proved that the overexpression of a small number of factors can push the cell to transition to a new stable state that is associated with changes in the activity of thousands of genes.[7]

Reprogramming mechanisms are thus linked, rather than independent and are centered on a small number of genes.[62] IPSC properties are very similar to ESCs.[63] iPSCs have been shown to support the development of all-iPSC mice using a tetraploid (4n) embryo,[64] the most stringent assay for developmental potential. However, some genetically normal iPSCs failed to produce all-iPSC mice because of aberrant epigenetic silencing of the imprinted Dlk1-Dio3 gene cluster.[18]

An important advantage of iPSC over ESC is that they can be derived from adult cells, rather than from embryos. Therefore, it became possible to obtain iPSC from adult and even elderly patients.[9][65][66]

Reprogramming somatic cells to iPSC leads to rejuvenation. It was found that reprogramming leads to telomere lengthening and subsequent shortening after their differentiation back into fibroblast-like derivatives.[67] Thus, reprogramming leads to the restoration of embryonic telomere length,[68] and hence increases the potential number of cell divisions otherwise limited by the Hayflick limit.[69]

However, because of the dissonance between rejuvenated cells and the surrounding niche of the recipient's older cells, the injection of his own iPSC usually leads to an immune response,[70] which can be used for medical purposes,[71] or the formation of tumors such as teratoma.[72] The reason has been hypothesized to be that some cells differentiated from ESC and iPSC in vivo continue to synthesize embryonic protein isoforms.[73] So, the immune system might detect and attack cells that are not cooperating properly.

A small molecule called MitoBloCK-6 can force the pluripotent stem cells to die by triggering apoptosis (via cytochrome c release across the mitochondrial outer membrane) in human pluripotent stem cells, but not in differentiated cells. Shortly after differentiation, daughter cells became resistant to death. When MitoBloCK-6 was introduced to differentiated cell lines, the cells remained healthy. The key to their survival, was hypothesized to be due to the changes undergone by pluripotent stem cell mitochondria in the process of cell differentiation. This ability of MitoBloCK-6 to separate the pluripotent and differentiated cell lines has the potential to reduce the risk of teratomas and other problems in regenerative medicine.[74]

In 2012 other small molecules (selective cytotoxic inhibitors of human pluripotent stem cellshPSCs) were identified that prevented human pluripotent stem cells from forming teratomas in mice. The most potent and selective compound of them (PluriSIn #1) inhibits stearoyl-coA desaturase (the key enzyme in oleic acid biosynthesis), which finally results in apoptosis. With the help of this molecule the undifferentiated cells can be selectively removed from culture.[75][76] An efficient strategy to selectively eliminate pluripotent cells with teratoma potential is targeting pluripotent stem cell-specific antiapoptotic factor(s) (i.e., survivin or Bcl10). A single treatment with chemical survivin inhibitors (e.g., quercetin or YM155) can induce selective and complete cell death of undifferentiated hPSCs and is claimed to be sufficient to prevent teratoma formation after transplantation.[77] However, it is unlikely that any kind of preliminary clearance,[78] is able to secure the replanting iPSC or ESC. After the selective removal of pluripotent cells, they re-emerge quickly by reverting differentiated cells into stem cells, which leads to tumors.[79] This may be due to the disorder of let-7 regulation of its target Nr6a1 (also known as Germ cell nuclear factor - GCNF), an embryonic transcriptional repressor of pluripotency genes that regulates gene expression in adult fibroblasts following micro-RNA miRNA loss.[80]

Teratoma formation by pluripotent stem cells may be caused by low activity of PTEN enzyme, reported to promote the survival of a small population (0,1-5% of total population) of highly tumorigenic, aggressive, teratoma-initiating embryonic-like carcinoma cells during differentiation. The survival of these teratoma-initiating cells is associated with failed repression of Nanog as well as a propensity for increased glucose and cholesterol metabolism.[81] These teratoma-initiating cells also expressed a lower ratio of p53/p21 when compared to non-tumorigenic cells.[82] In connection with the above safety problems, the use iPSC for cell therapy is still limited.[83] However, they can be used for a variety of other purposes - including the modeling of disease,[84] screening (selective selection) of drugs, toxicity testing of various drugs.[85]

It is interesting to note that the tissue grown from iPSCs, placed in the "chimeric" embryos in the early stages of mouse development, practically do not cause an immune response (after the embryos have grown into adult mice) and are suitable for autologous transplantation[86] At the same time, full reprogramming of adult cells in vivo within tissues by transitory induction of the four factors Oct4, Sox2, Klf4 and c-Myc in mice results in teratomas emerging from multiple organs.[51] Furthermore, partial reprogramming of cells toward pluripotency in vivo in mice demonstrates that incomplete reprogramming entails epigenetic changes (failed repression of Polycomb targets and altered DNA methylation) in cells that drive cancer development.[87]

Determining the unique set of cellular factors that is needed to be manipulated for each cell conversion is a long and costly process that involved much trial and error. As a result, this first step of identifying the key set of cellular factors for cell conversion is the major obstacle researchers face in the field of cell reprogramming. An international team of researchers have developed an algorithm, called Mogrify(1), that can predict the optimal set of cellular factors required to convert one human cell type to another. When tested, Mogrify was able to accurately predict the set of cellular factors required for previously published cell conversions correctly. To further validate Mogrify's predictive ability, the team conducted two novel cell conversions in the laboratory using human cells and these were successful in both attempts solely using the predictions of Mogrify.[89][90][91] Mogrify has been made available online for other researchers and scientists.

By using solely small molecules, Deng Hongkui and colleagues demonstrated that endogenous "master genes" are enough for cell fate reprogramming. They induced a pluripotent state in adult cells from mice using seven small-molecule compounds.[17] The effectiveness of the method is quite high: it was able to convert 0.02% of the adult tissue cells into iPSCs, which is comparable to the gene insertion conversion rate. The authors note that the mice generated from CiPSCs were "100% viable and apparently healthy for up to 6 months". So, this chemical reprogramming strategy has potential use in generating functional desirable cell types for clinical applications.[92][93]

In 2015th year a robust chemical reprogramming system was established with a yield up to 1,000-fold greater than that of the previously reported protocol. So, chemical reprogramming became a promising approach to manipulate cell fates.[94]

The fact that human iPSCs capable of forming teratomas not only in humans but also in some animal body, in particular in mice or pigs, allowed to develop a method for differentiation of iPSCs in vivo. For this purpose, iPSCs with an agent for inducing differentiation into target cells are injected to genetically modified pig or mouse that has suppressed immune system activation on human cells. The formed teratoma is cut out and used for the isolation of the necessary differentiated human cells[95] by means of monoclonal antibody to tissue-specific markers on the surface of these cells. This method has been successfully used for the production of functional myeloid, erythroid and lymphoid human cells suitable for transplantation (yet only to mice).[96] Mice engrafted with human iPSC teratoma-derived hematopoietic cells produced human B and T cells capable of functional immune responses. These results offer hope that in vivo generation of patient customized cells is feasible, providing materials that could be useful for transplantation, human antibody generation and drug screening applications. Using MitoBloCK-6[74] and/or PluriSIn # 1 the differentiated progenitor cells can be further purified from teratoma forming pluripotent cells. The fact, that the differentiation takes place even in the teratoma niche, offers hope that the resulting cells are sufficiently stable to stimuli able to cause their transition back to the dedifferentiated (pluripotent) state and therefore safe. A similar in vivo differentiation system, yielding engraftable hematopoietic stem cells from mouse and human iPSCs in teratoma-bearing animals in combination with a maneuver to facilitate hematopoiesis, was described by Suzuki et al.[97] They noted that neither leukemia nor tumors were observed in recipients after intravenous injection of iPSC-derived hematopoietic stem cells into irradiated recipients. Moreover, this injection resulted in multilineage and long-term reconstitution of the hematolymphopoietic system in serial transfers. Such system provides a useful tool for practical application of iPSCs in the treatment of hematologic and immunologic diseases.[98]

For further development of this method animal in which is grown the human cell graft, for example mouse, must have so modified genome that all its cells express and have on its surface human SIRP.[99] To prevent rejection after transplantation to the patient of the allogenic organ or tissue, grown from the pluripotent stem cells in vivo in the animal, these cells should express two molecules: CTLA4-Ig, which disrupts T cell costimulatory pathways and PD-L1, which activates T cell inhibitory pathway.[100]

See also: US 20130058900 patent.

In the near-future, clinical trials designed to demonstrate the safety of the use of iPSCs for cell therapy of the people with age-related macular degeneration, a disease causing blindness through retina damaging, will begin. There are several articles describing methods for producing retinal cells from iPSCs[101][102] and how to use them for cell therapy.[103][104] Reports of iPSC-derived retinal pigmented epithelium transplantation showed enhanced visual-guided behaviors of experimental animals for 6 weeks after transplantation.[105] However, clinical trials have been successful: ten patients suffering from retinitis pigmentosa have had their eyesight restoredincluding a woman who had only 17 percent of her vision left.[106]

Chronic lung diseases such as idiopathic pulmonary fibrosis and cystic fibrosis or chronic obstructive pulmonary disease and asthma are leading causes of morbidity and mortality worldwide with a considerable human, societal and financial burden. So there is an urgent need for effective cell therapy and lung tissue engineering.[107][108] Several protocols have been developed for generation of the most cell types of the respiratory system, which may be useful for deriving patient-specific therapeutic cells.[109][110][111][112][113]

Some lines of iPSCs have the potentiality to differentiate into male germ cells and oocyte-like cells in an appropriate niche (by culturing in retinoic acid and porcine follicular fluid differentiation medium or seminiferous tubule transplantation). Moreover, iPSC transplantation make a contribution to repairing the testis of infertile mice, demonstrating the potentiality of gamete derivation from iPSCs in vivo and in vitro.[114]

The risk of cancer and tumors creates the need to develop methods for safer cell lines suitable for clinical use. An alternative approach is so-called "direct reprogramming" - transdifferentiation of cells without passing through the pluripotent state.[115][116][117][118][119][120] The basis for this approach was that 5-azacytidine - a DNA demethylation reagent - can cause the formation of myogenic, chondrogenic and adipogeni clones in the immortal cell line of mouse embryonic fibroblasts[121] and that the activation of a single gene, later named MyoD1, is sufficient for such reprogramming.[122] Compared with iPSC whose reprogramming requires at least two weeks, the formation of induced progenitor cells sometimes occurs within a few days and the efficiency of reprogramming is usually many times higher. This reprogramming does not always require cell division.[123] The cells resulting from such reprogramming are more suitable for cell therapy because they do not form teratomas.[120] For example, Chandrakanthan et al., & Pimanda describe the generation of tissue-regenerative multipotent stem cells (iMS cells) by treating mature bone and fat cells transiently with a growth factor (platelet-derived growth factorAB (PDGF-AB)) and 5-Azacytidine. These authors claim that: "Unlike primary mesenchymal stem cells, which are used with little objective evidence in clinical practice to promote tissue repair, iMS cells contribute directly to in vivo tissue regeneration in a context-dependent manner without forming tumors" and so "has significant scope for application in tissue regeneration."[124][125][126]

Originally only early embryonic cells could be coaxed into changing their identity. Mature cells are resistant to changing their identity once they've committed to a specific kind. However, brief expression of a single transcription factor, the ELT-7 GATA factor, can convert the identity of fully differentiated, specialized non-endodermal cells of the pharynx into fully differentiated intestinal cells in intact larvae and adult roundworm Caenorhabditis elegans with no requirement for a dedifferentiated intermediate.[127]

The cell fate can be effectively manipulated by epigenome editing. In particular, by directly activating of specific endogenous gene expression with CRISPR-mediated activator. When dCas9 (that has been modified so that it no longer cuts DNA, but still can be guided to specific sequences and to bind to them) is combined with transcription activators, it can precisely manipulate endogenous gene expression. Using this method, Wei et al., enhanced the expression of endogenous Cdx2 and Gata6 genes by CRISPR-mediated activators, thus directly converted mouse embryonic stem cells into two extraembryonic lineages, i.e., typical trophoblast stem cells and extraembryonic endoderm cells.[128] An analogous approach was used to induce activation of the endogenous Brn2, Ascl1, and Myt1l genes to convert mouse embryonic fibroblasts to induced neuronal cells.[129] Thus, transcriptional activation and epigenetic remodeling of endogenous master transcription factors are sufficient for conversion between cell types. The rapid and sustained activation of endogenous genes in their native chromatin context by this approach may facilitate reprogramming with transient methods that avoid genomic integration and provides a new strategy for overcoming epigenetic barriers to cell fate specification.

Another way of reprogramming is the simulation of the processes that occur during amphibian limb regeneration. In urodele amphibians, an early step in limb regeneration is skeletal muscle fiber dedifferentiation into a cellulate that proliferates into limb tissue. However, sequential small molecule treatment of the muscle fiber with myoseverin, reversine (the aurora B kinase inhibitor) and some other chemicals: BIO (glycogen synthase-3 kinase inhibitor), lysophosphatidic acid (pleiotropic activator of G-protein-coupled receptors), SB203580 (p38 MAP kinase inhibitor), or SQ22536 (adenylyl cyclase inhibitor) causes the formation of new muscle cell types as well as other cell types such as precursors to fat, bone and nervous system cells.[130]

The researchers discovered that GCSF-mimicking antibody can activate a growth-stimulating receptor on marrow cells in a way that induces marrow stem cells that normally develop into white blood cells to become neural progenitor cells. The technique[131] enables researchers to search large libraries of antibodies and quickly select the ones with a desired biological effect.[132]

Schlegel and Liu[133] demonstrated that the combination of feeder cells[134][135][136] and a Rho kinase inhibitor (Y-27632) [137][138] induces normal and tumor epithelial cells from many tissues to proliferate indefinitely in vitro. This process occurs without the need for transduction of exogenous viral or cellular genes. These cells have been termed "Conditionally Reprogrammed Cells (CRC)". The induction of CRCs is rapid and results from reprogramming of the entire cell population. CRCs do not express high levels of proteins characteristic of iPSCs or embryonic stem cells (ESCs) (e.g., Sox2, Oct4, Nanog, or Klf4). This induction of CRCs is reversible and removal of Y-27632 and feeders allows the cells to differentiate normally.[133][139][140] CRC technology can generate 2106 cells in 5 to 6 days from needle biopsies and can generate cultures from cryopreserved tissue and from fewer than four viable cells. CRCs retain a normal karyotype and remain nontumorigenic. This technique also efficiently establishes cell cultures from human and rodent tumors.[133][141][142]

The ability to rapidly generate many tumor cells from small biopsy specimens and frozen tissue provides significant opportunities for cell-based diagnostics and therapeutics (including chemosensitivity testing) and greatly expands the value of biobanking.[133][141][142] Using CRC technology, researchers were able to identify an effective therapy for a patient with a rare type of lung tumor.[143] Engleman's group[144] describes a pharmacogenomic platform that facilitates rapid discovery of drug combinations that can overcome resistance using CRC system. In addition, the CRC method allows for the genetic manipulation of epithelial cells ex vivo and their subsequent evaluation in vivo in the same host. While initial studies revealed that co-culturing epithelial cells with Swiss 3T3 cells J2 was essential for CRC induction, with transwell culture plates, physical contact between feeders and epithelial cells is not required for inducing CRCs and more importantly that irradiation of the feeder cells is required for this induction. Consistent with the transwell experiments, conditioned medium induces and maintains CRCs, which is accompanied by a concomitant increase of cellular telomerase activity. The activity of the conditioned medium correlates directly with radiation-induced feeder cell apoptosis. Thus, conditional reprogramming of epithelial cells is mediated by a combination of Y-27632 and a soluble factor(s) released by apoptotic feeder cells.[145]

Riegel et al.[146] demonstrate that mouse ME cells isolated from normal mammary glands or from mouse mammary tumor virus (MMTV)-Neuinduced mammary tumors, can be cultured indefinitely as conditionally reprogrammed cells (CRCs). Cell surface progenitor-associated markers are rapidly induced in normal mouse ME-CRCs relative to ME cells. However, the expression of certain mammary progenitor subpopulations, such as CD49f+ ESA+ CD44+, drops significantly in later passages. Nevertheless, mouse ME-CRCs grown in a three-dimensional extracellular matrix gave rise to mammary acinar structures. ME-CRCs isolated from MMTV-Neu transgenic mouse mammary tumors express high levels of HER2/neu, as well as tumor-initiating cell markers, such as CD44+, CD49f+ and ESA+ (EpCam). These patterns of expression are sustained in later CRC passages. Early and late passage ME-CRCs from MMTV-Neu tumors that were implanted in the mammary fat pads of syngeneic or nude mice developed vascular tumors that metastasized within 6 weeks of transplantation. Importantly, the histopathology of these tumors was indistinguishable from that of the parental tumors that develop in the MMTV-Neu mice. Application of the CRC system to mouse mammary epithelial cells provides an attractive model system to study the genetics and phenotype of normal and transformed mouse epithelium in a defined culture environment and in vivo transplant studies.

A different approach to CRC is to inhibit CD47a membrane protein that is the thrombospondin-1 receptor. Loss of CD47 permits sustained proliferation of primary murine endothelial cells, increases asymmetric division and enables these cells to spontaneously reprogram to form multipotent embryoid body-like clusters. CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells in vitro and in vivo. Thrombospondin-1 is a key environmental signal that inhibits stem cell self-renewal via CD47. Thus, CD47 antagonists enable cell self-renewal and reprogramming by overcoming negative regulation of c-Myc and other stem cell transcription factors.[147] In vivo blockade of CD47 using an antisense morpholino increases survival of mice exposed to lethal total body irradiation due to increased proliferative capacity of bone marrow-derived cells and radioprotection of radiosensitive gastrointestinal tissues.[148]

Differentiated macrophages can self-renew in tissues and expand long-term in culture.[27] Under certain conditions macrophages can divide without losing features they have acquired while specializing into immune cells - which is usually not possible with differentiated cells. The macrophages achieve this by activating a gene network similar to one found in embryonic stem cells. Single-cell analysis revealed that, in vivo, proliferating macrophages can derepress a macrophage-specific enhancer repertoire associated with a gene network controlling self-renewal. This happened when concentrations of two transcription factors named MafB and c-Maf were naturally low or were inhibited for a short time. Genetic manipulations that turned off MafB and c-Maf in the macrophages caused the cells to start a self-renewal program. The similar network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers.[28]

Hence macrophages isolated from MafB- and c-Maf-double deficient mice divide indefinitely; the self-renewal depends on c-Myc and Klf4.[149]

Indirect lineage conversion is a reprogramming methodology in which somatic cells transition through a plastic intermediate state of partially reprogrammed cells (pre-iPSC), induced by brief exposure to reprogramming factors, followed by differentiation in a specially developed chemical environment (artificial niche).[150]

This method could be both more efficient and safer, since it does not seem to produce tumors or other undesirable genetic changes and results in much greater yield than other methods. However, the safety of these cells remains questionable. Since lineage conversion from pre-iPSC relies on the use of iPSC reprogramming conditions, a fraction of the cells could acquire pluripotent properties if they do not stop the de-differentation process in vitro or due to further de-differentiation in vivo.[151]

A common feature of pluripotent stem cells is the specific nature of protein glycosylation of their outer membrane. That distinguishes them from most nonpluripotent cells, although not white blood cells.[152] The glycans on the stem cell surface respond rapidly to alterations in cellular state and signaling and are therefore ideal for identifying even minor changes in cell populations. Many stem cell markers are based on cell surface glycan epitopes including the widely used markers SSEA-3, SSEA-4, Tra 1-60 and Tra 1-81.[153] Suila Heli et al.[154] speculate that in human stem cells extracellular O-GlcNAc and extracellular O-LacNAc, play a crucial role in the fine tuning of Notch signaling pathway - a highly conserved cell signaling system, that regulates cell fate specification, differentiation, leftright asymmetry, apoptosis, somitogenesis, angiogenesis and plays a key role in stem cell proliferation (reviewed by Perdigoto and Bardin[155] and Jafar-Nejad et al.[156])

Changes in outer membrane protein glycosylation are markers of cell states connected in some way with pluripotency and differentiation.[157] The glycosylation change is apparently not just the result of the initialization of gene expression, but perform as an important gene regulator involved in the acquisition and maintenance of the undifferentiated state.[158]

For example, activation of glycoprotein ACA,[159] linking glycosylphosphatidylinositol on the surface of the progenitor cells in human peripheral blood, induces increased expression of genes Wnt, Notch-1, BMI1 and HOXB4 through a signaling cascade PI3K/Akt/mTor/PTEN and promotes the formation of a self-renewing population of hematopoietic stem cells.[160]

Furthermore, dedifferentiation of progenitor cells induced by ACA-dependent signaling pathway leads to ACA-induced pluripotent stem cells, capable of differentiating in vitro into cells of all three germ layers.[161] The study of lectins' ability to maintain a culture of pluripotent human stem cells has led to the discovery of lectin Erythrina crista-galli (ECA), which can serve as a simple and highly effective matrix for the cultivation of human pluripotent stem cells.[162]

Cell adhesion protein E-cadherin is indispensable for a robust pluripotent phenotype.[163] During reprogramming for iPS cell generation, N-cadherin can replace function of E-cadherin.[164] These functions of cadherins are not directly related to adhesion because sphere morphology helps maintaining the "stemness" of stem cells.[165] Moreover, sphere formation, due to forced growth of cells on a low attachment surface, sometimes induces reprogramming. For example, neural progenitor cells can be generated from fibroblasts directly through a physical approach without introducing exogenous reprogramming factors.

Physical cues, in the form of parallel microgrooves on the surface of cell-adhesive substrates, can replace the effects of small-molecule epigenetic modifiers and significantly improve reprogramming efficiency. The mechanism relies on the mechanomodulation of the cells' epigenetic state. Specifically, "decreased histone deacetylase activity and upregulation of the expression of WD repeat domain 5 (WDR5)a subunit of H3 methyltranferaseby microgrooved surfaces lead to increased histone H3 acetylation and methylation". Nanofibrous scaffolds with aligned fibre orientation produce effects similar to those produced by microgrooves, suggesting that changes in cell morphology may be responsible for modulation of the epigenetic state.[166]

Substrate rigidity is an important biophysical cue influencing neural induction and subtype specification. For example, soft substrates promote neuroepithelial conversion while inhibiting neural crest differentiation of hESCs in a BMP4-dependent manner. Mechanistic studies revealed a multi-targeted mechanotransductive process involving mechanosensitive Smad phosphorylation and nucleocytoplasmic shuttling, regulated by rigidity-dependent Hippo/YAP activities and actomyosin cytoskeleton integrity and contractility.[167]

Mouse embryonic stem cells (mESCs) undergo self-renewal in the presence of the cytokine leukemia inhibitory factor (LIF). Following LIF withdrawal, mESCs differentiate, accompanied by an increase in cellsubstratum adhesion and cell spreading. Restricted cell spreading in the absence of LIF by either culturing mESCs on chemically defined, weakly adhesive biosubstrates, or by manipulating the cytoskeleton allowed the cells to remain in an undifferentiated and pluripotent state. The effect of restricted cell spreading on mESC self-renewal is not mediated by increased intercellular adhesion, as inhibition of mESC adhesion using a function blocking anti E-cadherin antibody or siRNA does not promote differentiation.[168] Possible mechanisms of stem cell fate predetermination by physical interactions with the extracellular matrix have been described.[169][170]

A new method has been developed that turns cells into stem cells faster and more efficiently by 'squeezing' them using 3D microenvironment stiffness and density of the surrounding gel. The technique can be applied to a large number of cells to produce stem cells for medical purposes on an industrial scale.[171][172]

Cells involved in the reprogramming process change morphologically as the process proceeds. This results in physical difference in adhesive forces among cells. Substantial differences in 'adhesive signature' between pluripotent stem cells, partially reprogrammed cells, differentiated progeny and somatic cells allowed to develop separation process for isolation of pluripotent stem cells in microfluidic devices,[173] which is:

Stem cells possess mechanical memory (they remember past physical signals)with the Hippo signaling pathway factors:[174] Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ) acting as an intracellular mechanical rheostatthat stores information from past physical environments and influences the cells' fate.[175][176]

Stroke and many neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis need cell replacement therapy. The successful use of converted neural cells (cNs) in transplantations open a new avenue to treat such diseases.[177] Nevertheless, induced neurons (iNs), directly converted from fibroblasts are terminally committed and exhibit very limited proliferative ability that may not provide enough autologous donor cells for transplantation.[178] Self-renewing induced neural stem cells (iNSCs) provide additional advantages over iNs for both basic research and clinical applications.[118][119][120][179][180]

For example, under specific growth conditions, mouse fibroblasts can be reprogrammed with a single factor, Sox2, to form iNSCs that self-renew in culture and after transplantation can survive and integrate without forming tumors in mouse brains.[181] INSCs can be derived from adult human fibroblasts by non-viral techniques, thus offering a safe method for autologous transplantation or for the development of cell-based disease models.[180]

Neural chemically induced progenitor cells (ciNPCs) can be generated from mouse tail-tip fibroblasts and human urinary somatic cells without introducing exogenous factors, but - by a chemical cocktail, namely VCR (V, VPA, an inhibitor of HDACs; C, CHIR99021, an inhibitor of GSK-3 kinases and R, RepSox, an inhibitor of TGF beta signaling pathways), under a physiological hypoxic condition.[182] Alternative cocktails with inhibitors of histone deacetylation, glycogen synthase kinase and TGF- pathways (where: sodium butyrate (NaB) or Trichostatin A (TSA) could replace VPA, Lithium chloride (LiCl) or lithium carbonate (Li2CO3) could substitute CHIR99021, or Repsox may be replaced with SB-431542 or Tranilast) show similar efficacies for ciNPC induction.[182] Zhang, et al.,[183] also report highly efficient reprogramming of mouse fibroblasts into induced neural stem cell-like cells (ciNSLCs) using a cocktail of nine components.

Multiple methods of direct transformation of somatic cells into induced neural stem cells have been described.[184]

Proof of principle experiments demonstrate that it is possible to convert transplanted human fibroblasts and human astrocytes directly in the brain that are engineered to express inducible forms of neural reprogramming genes, into neurons, when reprogramming genes (Ascl1, Brn2a and Myt1l) are activated after transplantation using a drug.[185]

Astrocytesthe most common neuroglial brain cells, which contribute to scar formation in response to injurycan be directly reprogrammed in vivo to become functional neurons that formed networks in mice without the need of cell transplantation.[186] The researchers followed the mice for nearly a year to look for signs of tumor formation and reported finding none. The same researchers have turned scar-forming astrocytes into progenitor cells called neuroblasts that regenerated into neurons in the injured adult spinal cord.[187]

Without myelin to insulate neurons, nerve signals quickly lose power. Diseases that attack myelin, such as multiple sclerosis, result in nerve signals that cannot propagate to nerve endings and as a consequence lead to cognitive, motor and sensory problems. Transplantation of oligodendrocyte precursor cells (OPCs), which can successfully create myelin sheaths around nerve cells, is a promising potential therapeutic response. Direct lineage conversion of mouse and rat fibroblasts into oligodendroglial cells provides a potential source of OPCs. Conversion by forced expression of both eight[188] or of the three[189] transcription factors Sox10, Olig2 and Zfp536, may provide such cells.

Cell-based in vivo therapies may provide a transformative approach to augment vascular and muscle growth and to prevent non-contractile scar formation by delivering transcription factors[115] or microRNAs[14] to the heart.[190] Cardiac fibroblasts, which represent 50% of the cells in the mammalian heart, can be reprogrammed into cardiomyocyte-like cells in vivo by local delivery of cardiac core transcription factors ( GATA4, MEF2C, TBX5 and for improved reprogramming plus ESRRG, MESP1, Myocardin and ZFPM2) after coronary ligation.[115][191] These results implicated therapies that can directly remuscularize the heart without cell transplantation. However, the efficiency of such reprogramming turned out to be very low and the phenotype of received cardiomyocyte-like cells does not resemble those of a mature normal cardiomyocyte. Furthermore, transplantation of cardiac transcription factors into injured murine hearts resulted in poor cell survival and minimal expression of cardiac genes.[192]

Meanwhile, advances in the methods of obtaining cardiac myocytes in vitro occurred.[193][194] Efficient cardiac differentiation of human iPS cells gave rise to progenitors that were retained within infarcted rat hearts and reduced remodeling of the heart after ischemic damage.[195]

The team of scientists, who were led by Sheng Ding, used a cocktail of nine chemicals (9C) for transdifferentiation of human skin cells into beating heart cells. With this method, more than 97% of the cells began beating, a characteristic of fully developed, healthy heart cells. The chemically induced cardiomyocyte-like cells (ciCMs) uniformly contracted and resembled human cardiomyocytes in their transcriptome, epigenetic, and electrophysiological properties. When transplanted into infarcted mouse hearts, 9C-treated fibroblasts were efficiently converted to ciCMs and developed into healthy-looking heart muscle cells within the organ.[196] This chemical reprogramming approach, after further optimization, may offer an easy way to provide the cues that induce heart muscle to regenerate locally.[197]

In another study, ischemic cardiomyopathy in the murine infarction model was targeted by iPS cell transplantation. It synchronized failing ventricles, offering a regenerative strategy to achieve resynchronization and protection from decompensation by dint of improved left ventricular conduction and contractility, reduced scarring and reversal of structural remodelling.[198] One protocol generated populations of up to 98% cardiomyocytes from hPSCs simply by modulating the canonical Wnt signaling pathway at defined time points in during differentiation, using readily accessible small molecule compounds.[199]

Discovery of the mechanisms controlling the formation of cardiomyocytes led to the development of the drug ITD-1, which effectively clears the cell surface from TGF- receptor type II and selectively inhibits intracellular TGF- signaling. It thus selectively enhances the differentiation of uncommitted mesoderm to cardiomyocytes, but not to vascular smooth muscle and endothelial cells.[200]

One project seeded decellularized mouse hearts with human iPSC-derived multipotential cardiovascular progenitor cells. The introduced cells migrated, proliferated and differentiated in situ into cardiomyocytes, smooth muscle cells and endothelial cells to reconstruct the hearts. In addition, the heart's extracellular matrix (the substrate of heart scaffold) signalled the human cells into becoming the specialised cells needed for proper heart function. After 20 days of perfusion with growth factors, the engineered heart tissues started to beat again and were responsive to drugs.[201]

Reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells (iCMs) in situ represents a promising strategy for cardiac regeneration. Mice exposed in vivo, to three cardiac transcription factors GMT (Gata4, Mef2c, Tbx5) and the small-molecules: SB-431542 (the transforming growth factor (TGF)- inhibitor), and XAV939 (the WNT inhibitor) for 2 weeks after myocardial infarction showed significantly improved reprogramming (reprogramming efficiency increased eight-fold) and cardiac function compared to those exposed to only GMT.[202]

See also: review[203]

The elderly often suffer from progressive muscle weakness and regenerative failure owing in part to elevated activity of the p38 and p38 mitogen-activated kinase pathway in senescent skeletal muscle stem cells. Subjecting such stem cells to transient inhibition of p38 and p38 in conjunction with culture on soft hydrogel substrates rapidly expands and rejuvenates them that result in the return of their strength.[204]

In geriatric mice, resting satellite cells lose reversible quiescence by switching to an irreversible pre-senescence state, caused by derepression of p16INK4a (also called Cdkn2a). On injury, these cells fail to activate and expand, even in a youthful environment. p16INK4a silencing in geriatric satellite cells restores quiescence and muscle regenerative functions.[205]

Myogenic progenitors for potential use in disease modeling or cell-based therapies targeting skeletal muscle could also be generated directly from induced pluripotent stem cells using free-floating spherical culture (EZ spheres) in a culture medium supplemented with high concentrations (100ng/ml) of fibroblast growth factor-2 (FGF-2) and epidermal growth factor.[206]

Unlike current protocols for deriving hepatocytes from human fibroblasts, Saiyong Zhu et al., (2014)[207] did not generate iPSCs but, using small molecules, cut short reprogramming to pluripotency to generate an induced multipotent progenitor cell (iMPC) state from which endoderm progenitor cells and subsequently hepatocytes (iMPC-Heps) were efficiently differentiated. After transplantation into an immune-deficient mouse model of human liver failure, iMPC-Heps proliferated extensively and acquired levels of hepatocyte function similar to those of human primary adult hepatocytes. iMPC-Heps did not form tumours, most probably because they never entered a pluripotent state.

These results establish the feasibility of significant liver repopulation of mice with human hepatocytes generated in vitro, which removes a long-standing roadblock on the path to autologous liver cell therapy.

Cocktail of small molecules, Y-27632, A-83-01 (a TGF kinase/activin receptor like kinase (ALK5) inhibitor), and CHIR99021 (potent inhibitor of GSK-3), can convert rat and mouse mature hepatocytes in vitro into proliferative bipotent cells - CLiPs (chemically induced liver progenitors). CLiPs can differentiate into both mature hepatocytes and biliary epithelial cells that can form functional ductal structures. In long-term culture CLiPs did not lose their proliferative capacity and their hepatic differentiation ability, and can repopulate chronically injured liver tissue.[208]

Complications of Diabetes mellitus such as cardiovascular diseases, retinopathy, neuropathy, nephropathy and peripheral circulatory diseases depend on sugar dysregulation due to lack of insulin from pancreatic beta cells and can be lethal if they are not treated. One of the promising approaches to understand and cure diabetes is to use pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced PCSs (iPSCs).[209] Unfortunately, human PSC-derived insulin-expressing cells resemble human fetal cells rather than adult cells. In contrast to adult cells, fetal cells seem functionally immature, as indicated by increased basal glucose secretion and lack of glucose stimulation and confirmed by RNA-seq of whose transcripts.[210]

An alternative strategy is the conversion of fibroblasts towards distinct endodermal progenitor cell populations and, using cocktails of signalling factors, successful differentiation of these endodermal progenitor cells into functional beta-like cells both in vitro and in vivo.[211]

Overexpression of the three transcription factors, PDX1 (required for pancreatic bud outgrowth and beta-cell maturation), NGN3 (required for endocrine precursor cell formation) and MAFA (for beta-cell maturation) combination (called PNM) can lead to the transformation of some cell types into a beta cell-like state.[212] An accessible and abundant source of functional insulin-producing cells is intestine. PMN expression in human intestinal "organoids" stimulates the conversion of intestinal epithelial cells into -like cells possibly acceptable for transplantation.[213]

Adult proximal tubule cells were directly transcriptionally reprogrammed to nephron progenitors of the embryonic kidney, using a pool of six genes of instructive transcription factors (SIX1, SIX2, OSR1, Eyes absent homolog 1(EYA1), Homeobox A11 (HOXA11) and Snail homolog 2 (SNAI2)) that activated genes consistent with a cap mesenchyme/nephron progenitor phenotype in the adult proximal tubule cell line.[214] The generation of such cells may lead to cellular therapies for adult renal disease. Embryonic kidney organoids placed into adult rat kidneys can undergo onward development and vascular development.[215]

As blood vessels age, they often become abnormal in structure and function, thereby contributing to numerous age-associated diseases including myocardial infarction, ischemic stroke and atherosclerosis of arteries supplying the heart, brain and lower extremities. So, an important goal is to stimulate vascular growth for the collateral circulation to prevent the exacerbation of these diseases. Induced Vascular Progenitor Cells (iVPCs) are useful for cell-based therapy designed to stimulate coronary collateral growth. They were generated by partially reprogramming endothelial cells.[150] The vascular commitment of iVPCs is related to the epigenetic memory of endothelial cells, which engenders them as cellular components of growing blood vessels. That is why, when iVPCs were implanted into myocardium, they engrafted in blood vessels and increased coronary collateral flow better than iPSCs, mesenchymal stem cells, or native endothelial cells.[216]

Ex vivo genetic modification can be an effective strategy to enhance stem cell function. For example, cellular therapy employing genetic modification with Pim-1 kinase (a downstream effector of Akt, which positively regulates neovasculogenesis) of bone marrowderived cells[217] or human cardiac progenitor cells, isolated from failing myocardium[218] results in durability of repair, together with the improvement of functional parameters of myocardial hemodynamic performance.

Stem cells extracted from fat tissue after liposuction may be coaxed into becoming progenitor smooth muscle cells (iPVSMCs) found in arteries and veins.[219]

The 2D culture system of human iPS cells[220] in conjunction with triple marker selection (CD34 (a surface glycophosphoprotein expressed on developmentally early embryonic fibroblasts), NP1 (receptor - neuropilin 1) and KDR (kinase insert domain-containing receptor)) for the isolation of vasculogenic precursor cells from human iPSC, generated endothelial cells that, after transplantation, formed stable, functional mouse blood vessels in vivo, lasting for 280 days.[221]

To treat infarction, it is important to prevent the formation of fibrotic scar tissue. This can be achieved in vivo by transient application of paracrine factors that redirect native heart progenitor stem cell contributions from scar tissue to cardiovascular tissue. For example, in a mouse myocardial infarction model, a single intramyocardial injection of human vascular endothelial growth factor A mRNA (VEGF-A modRNA), modified to escape the body's normal defense system, results in long-term improvement of heart function due to mobilization and redirection of epicardial progenitor cells toward cardiovascular cell types.[222]

RBC transfusion is necessary for many patients. However, to date the supply of RBCs remains labile. In addition, transfusion risks infectious disease transmission. A large supply of safe RBCs generated in vitro would help to address this issue. Ex vivo erythroid cell generation may provide alternative transfusion products to meet present and future clinical requirements.[223][224] Red blood cells (RBC)s generated in vitro from mobilized CD34 positive cells have normal survival when transfused into an autologous recipient.[225] RBC produced in vitro contained exclusively fetal hemoglobin (HbF), which rescues the functionality of these RBCs. In vivo the switch of fetal to adult hemoglobin was observed after infusion of nucleated erythroid precursors derived from iPSCs.[226] Although RBCs do not have nuclei and therefore can not form a tumor, their immediate erythroblasts precursors have nuclei. The terminal maturation of erythroblasts into functional RBCs requires a complex remodeling process that ends with extrusion of the nucleus and the formation of an enucleated RBC.[227] Cell reprogramming often disrupts enucleation. Transfusion of in vitro-generated RBCs or erythroblasts does not sufficiently protect against tumor formation.

The aryl hydrocarbon receptor (AhR) pathway (which has been shown to be involved in the promotion of cancer cell development) plays an important role in normal blood cell development. AhR activation in human hematopoietic progenitor cells (HPs) drives an unprecedented expansion of HPs, megakaryocyte- and erythroid-lineage cells.[228] See also Concise Review:[229][230] The SH2B3 gene encodes a negative regulator of cytokine signaling and naturally occurring loss-of-function variants in this gene increase RBC counts in vivo. Targeted suppression of SH2B3 in primary human hematopoietic stem and progenitor cells enhanced the maturation and overall yield of in-vitro-derived RBCs. Moreover, inactivation of SH2B3 by CRISPR/Cas9 genome editing in human pluripotent stem cells allowed enhanced erythroid cell expansion with preserved differentiation.[231] (See also overview.[230][232])

Platelets help prevent hemorrhage in thrombocytopenic patients and patients with thrombocythemia. A significant problem for multitransfused patients is refractoriness to platelet transfusions. Thus, the ability to generate platelet products ex vivo and platelet products lacking HLA antigens in serum-free media would have clinical value. An RNA interference-based mechanism used a lentiviral vector to express short-hairpin RNAi targeting 2-microglobulin transcripts in CD34-positive cells. Generated platelets demonstrated an 85% reduction in class I HLA antigens. These platelets appeared to have normal function in vitro[233]

One clinically-applicable strategy for the derivation of functional platelets from human iPSC involves the establishment of stable immortalized megakaryocyte progenitor cell lines (imMKCLs) through doxycycline-dependent overexpression of BMI1 and BCL-XL. The resulting imMKCLs can be expanded in culture over extended periods (45 months), even after cryopreservation. Halting the overexpression (by the removal of doxycycline from the medium) of c-MYC, BMI1 and BCL-XL in growing imMKCLs led to the production of CD42b+ platelets with functionality comparable to that of native platelets on the basis of a range of assays in vitro and in vivo.[234] Thomas et al., describe a forward programming strategy relying on the concurrent exogenous expression of 3 transcription factors: GATA1, FLI1 and TAL1. The forward programmed megakaryocytes proliferate and differentiate in culture for several months with megakaryocyte purity over 90% reaching up to 2x105 mature megakaryocytes per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as one million starting hPSCs.[235] See also overview[236]

A specialised type of white blood cell, known as cytotoxic T lymphocytes (CTLs), are produced by the immune system and are able to recognise specific markers on the surface of various infectious or tumour cells, causing them to launch an attack to kill the harmful cells. Thence, immunotherapy with functional antigen-specific T cells has potential as a therapeutic strategy for combating many cancers and viral infections.[237] However, cell sources are limited, because they are produced in small numbers naturally and have a short lifespan.

A potentially efficient approach for generating antigen-specific CTLs is to revert mature immune T cells into iPSCs, which possess indefinite proliferative capacity in vitro and after their multiplication to coax them to redifferentiate back into T cells.[238][239][240]

Another method combines iPSC and chimeric antigen receptor (CAR)[241] technologies to generate human T cells targeted to CD19, an antigen expressed by malignant B cells, in tissue culture.[242] This approach of generating therapeutic human T cells may be useful for cancer immunotherapy and other medical applications.

Invariant natural killer T (iNKT) cells have great clinical potential as adjuvants for cancer immunotherapy. iNKT cells act as innate T lymphocytes and serve as a bridge between the innate and acquired immune systems. They augment anti-tumor responses by producing interferon-gamma (IFN-).[243] The approach of collection, reprogramming/dedifferentiation, re-differentiation and injection has been proposed for related tumor treatment.[244]

Dendritic cells (DC) are specialized to control T-cell responses. DC with appropriate genetic modifications may survive long enough to stimulate antigen-specific CTL and after that be completely eliminated. DC-like antigen-presenting cells obtained from human induced pluripotent stem cells can serve as a source for vaccination therapy.[245]

CCAAT/enhancer binding protein- (C/EBP) induces transdifferentiation of B cells into macrophages at high efficiencies[246] and enhances reprogramming into iPS cells when co-expressed with transcription factors Oct4, Sox2, Klf4 and Myc.[247] with a 100-fold increase in iPS cell reprogramming efficiency, involving 95% of the population.[248] Furthermore, C/EBPa can convert selected human B cell lymphoma and leukemia cell lines into macrophage-like cells at high efficiencies, impairing the cells' tumor-forming capacity.[249]

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Induced stem cells - Wikipedia

Cardiac Stem Cells Comments Off on Induced stem cells – Wikipedia | November 28th, 2016

An isolated cardiac muscle cell, beating

Cardiac muscle (heart muscle) is an involuntary, striated muscle that is found in the walls and histological foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle. These three types of muscle all form in the process of myogenesis. The cells that constitute cardiac muscle, called cardiomyocytes or myocardiocytes, predominantly contain only one nucleus, although populations with two to four nuclei do exist.[1][2][pageneeded] The myocardium is the muscle tissue of the heart, and forms a thick middle layer between the outer epicardium layer and the inner endocardium layer.

Coordinated contractions of cardiac muscle cells in the heart pump blood out of the atria and ventricles to the blood vessels of the left/body/systemic and right/lungs/pulmonary circulatory systems. This complex mechanism illustrates systole of the heart.

Cardiac muscle cells, unlike most other tissues in the body, rely on an available blood and electrical supply to deliver oxygen and nutrients and remove waste products such as carbon dioxide. The coronary arteries help fulfill this function.

Cardiac muscle has cross striations formed by rotating segments of thick and thin protein filaments. Like skeletal muscle, the primary structural proteins of cardiac muscle are myosin and actin. The actin filaments are thin, causing the lighter appearance of the I bands in striated muscle, whereas the myosin filament is thicker, lending a darker appearance to the alternating A bands as observed with electron microscopy. However, in contrast to skeletal muscle, cardiac muscle cells are typically branch-like instead of linear.

Another histological difference between cardiac muscle and skeletal muscle is that the T-tubules in the cardiac muscle are bigger and wider and track laterally to the Z-discs. There are fewer T-tubules in comparison with skeletal muscle. The diad is a structure in the cardiac myocyte located at the sarcomere Z-line. It is composed of a single T-tubule paired with a terminal cisterna of the sarcoplasmic reticulum. The diad plays an important role in excitation-contraction coupling by juxtaposing an inlet for the action potential near a source of Ca2+ ions. This way, the wave of depolarization can be coupled to calcium-mediated cardiac muscle contraction via the sliding filament mechanism. Cardiac muscle forms these instead of the triads formed between the sarcoplasmic reticulum in skeletal muscle and T-tubules. T-tubules play critical role in excitation-contraction coupling (ECC). Recently, the action potentials of T-tubules were recorded optically by Guixue Bu et al.[3]

The cardiac syncytium is a network of cardiomyocytes connected to each other by intercalated discs that enable the rapid transmission of electrical impulses through the network, enabling the syncytium to act in a coordinated contraction of the myocardium. There is an atrial syncytium and a ventricular syncytium that are connected by cardiac connection fibres.[4] Electrical resistance through intercalated discs is very low, thus allowing free diffusion of ions. The ease of ion movement along cardiac muscle fibers axes is such that action potentials are able to travel from one cardiac muscle cell to the next, facing only slight resistance. Each syncytium obeys the all or none law.[5]

Intercalated discs are complex adhering structures that connect the single cardiomyocytes to an electrochemical syncytium (in contrast to the skeletal muscle, which becomes a multicellular syncytium during mammalian embryonic development). The discs are responsible mainly for force transmission during muscle contraction. Intercalated discs consist of three different types of cell-cell junctions: the actin filament anchoring adherens junctions, the intermediate filament anchoring desmosomes , and gap junctions. They allow action potentials to spread between cardiac cells by permitting the passage of ions between cells, producing depolarization of the heart muscle. However, novel molecular biological and comprehensive studies unequivocally showed that intercalated discs consist for the most part of mixed-type adhering junctions named area composita (pl. areae compositae) representing an amalgamation of typical desmosomal and fascia adhaerens proteins (in contrast to various epithelia).[6][7][8] The authors discuss the high importance of these findings for the understanding of inherited cardiomyopathies (such as arrhythmogenic right ventricular cardiomyopathy).

Under light microscopy, intercalated discs appear as thin, typically dark-staining lines dividing adjacent cardiac muscle cells. The intercalated discs run perpendicular to the direction of muscle fibers. Under electron microscopy, an intercalated disc's path appears more complex. At low magnification, this may appear as a convoluted electron dense structure overlying the location of the obscured Z-line. At high magnification, the intercalated disc's path appears even more convoluted, with both longitudinal and transverse areas appearing in longitudinal section.[9]

In contrast to skeletal muscle, cardiac muscle requires extracellular calcium ions for contraction to occur. Like skeletal muscle, the initiation and upshoot of the action potential in ventricular cardiomyocytes is derived from the entry of sodium ions across the sarcolemma in a regenerative process. However, an inward flux of extracellular calcium ions through L-type calcium channels sustains the depolarization of cardiac muscle cells for a longer duration. The reason for the calcium dependence is due to the mechanism of calcium-induced calcium release (CICR) from the sarcoplasmic reticulum that must occur during normal excitation-contraction (EC) coupling to cause contraction. Once the intracellular concentration of calcium increases, calcium ions bind to the protein troponin, which allows myosin to bind to actin and contraction to occur.

Until recently, it was commonly believed that cardiac muscle cells could not be regenerated. However, a study reported in the April 3, 2009 issue of Science contradicts that belief.[10] Olaf Bergmann and his colleagues at the Karolinska Institute in Stockholm tested samples of heart muscle from people born before 1955 who had very little cardiac muscle around their heart, many showing with disabilities from this abnormality. By using DNA samples from many hearts, the researchers estimated that a 4-year-old renews about 20% of heart muscle cells per year, and about 69 percent of the heart muscle cells of a 50-year-old were generated after he or she was born.

One way that cardiomyocyte regeneration occurs is through the division of pre-existing cardiomyocytes during the normal aging process.[11] The division process of pre-existing cardiomyocytes has also been shown to increase in areas adjacent to sites of myocardial injury. In addition, certain growth factors promote the self-renewal of endogenous cardiomyocytes and cardiac stem cells. For example, insulin-like growth factor 1, hepatocyte growth factor, and high-mobility group protein B1 increase cardiac stem cell migration to the affected area, as well as the proliferation and survival of these cells.[12] Some members of the fibroblast growth factor family also induce cell-cycle re-entry of small cardiomyocytes. Vascular endothelial growth factor also plays an important role in the recruitment of native cardiac cells to an infarct site in addition to its angiogenic effect.

Based on the natural role of stem cells in cardiomyocyte regeneration, researchers and clinicians are increasingly interested in using these cells to induce regeneration of damaged tissue. Various stem cell lineages have been shown to be able to differentiate into cardiomyocytes, including bone marrow stem cells. For example, in one study, researchers transplanted bone marrow cells, which included a population of stem cells, adjacent to an infarct site in a mouse model. Nine days after surgery, the researchers found a new band of regenerating myocardium.[13] However, this regeneration was not observed when the injected population of cells was devoid of stem cells, which strongly suggests that it was the stem cell population that contributed to the myocardium regeneration. Other clinical trials have shown that autologous bone marrow cell transplants delivered via the infarct-related artery decreases the infarct area compared to patients not given the cell therapy.[14]

Occlusion (blockage) of the coronary arteries by atherosclerosis and/or thrombosis can lead to myocardial infarction (heart attack), where part of the myocardium is injured due to ischemia (not receiving enough oxygen). This occurs because coronary arteries are functional end arteries - i.e. there is almost no overlap in the areas supplied by different arteries (anastomoses) so that if one fails, others cannot adequately perfuse the region, unlike in other tissues.

Certain viruses lead to myocarditis (inflammation of the myocardium). Cardiomyopathies are inherent diseases of the myocardium, many of which are caused by genetic mutations.

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Cardiac muscle - Wikipedia

Cardiac Stem Cells Comments Off on Cardiac muscle – Wikipedia | November 27th, 2016

SIGNIFICANCE:

Heart disease is the primary cause of death in the industrialized world. Cardiac failure is dictated by an uncompensated reduction in the number of viable and fully functional cardiomyocytes. While current pharmacological therapies alleviate the symptoms associated with cardiac deterioration, heart transplantation remains the only therapy for advanced heart failure. Therefore, there is a pressing need for novel therapeutic modalities. Cell-based therapies involving cardiac stem cells (CSCs) constitute a promising emerging approach for the replenishment of the lost tissue and the restoration of cardiac contractility.

CSCs reside in the adult heart and govern myocardial homeostasis and repair after injury by producing new cardiomyocytes and vascular structures. In the last decade, different classes of immature cells expressing distinct stem cell markers have been identified and characterized in terms of their growth properties, differentiation potential, and regenerative ability. Phase I clinical trials, employing autologous CSCs in patients with ischemic cardiomyopathy, are being completed with encouraging results.

Accumulating evidence concerning the role of CSCs in heart regeneration imposes a reconsideration of the mechanisms of cardiac aging and the etiology of heart failure. Deciphering the molecular pathways that prevent activation of CSCs in their environment and understanding the processes that affect CSC survival and regenerative function with cardiac pathologies, commonly accompanied by alterations in redox conditions, are of great clinical importance.

Further investigations of CSC biology may be translated into highly effective and novel therapeutic strategies aiming at the enhancement of the endogenous healing capacity of the diseased heart.

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Cardiac stem cells: biology and clinical applications.

Cardiac Stem Cells Comments Off on Cardiac stem cells: biology and clinical applications. | November 7th, 2016

You have accessRestricted access

Article

The membrane scaffold SLP2 anchors a proteolytic hub in mitochondria containing PARL and the iAAA protease YME1L

These authors contributed equally to this work

The membrane scaffold SLP2 anchors a large protease complex containing the rhomboid protease PARL and the iAAA protease YME1L in the inner membrane of mitochondria, termed the SPY complex. Assembly into the SPY complex modulates PARL activity toward its substrate proteins PINK1 and PGAM5.

The membrane scaffold SLP2 anchors a large protease complex containing the rhomboid protease PARL and the iAAA protease YME1L in the inner membrane of mitochondria, termed the SPY complex. Assembly into the SPY complex modulates PARL activity toward its substrate proteins PINK1 and PGAM5.

SLP2 assembles with PARL and YME1L into the SPY complex in the mitochondrial inner membrane.

Assembly into SPY complexes modulates PARLmediated processing of PINK1 and PGAM5.

SLP2 restricts OMA1mediated processing of the OPA1.

Timothy Wai, Shotaro Saita, Hendrik Nolte, Sebastian Mller, Tim Knig, Ricarda RichterDennerlein, HansGeorg Sprenger, Joaquin Madrenas, Mareike Mhlmeister, Ulrich Brandt, Marcus Krger, Thomas Langer

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Home | EMBO Reports

Cardiac Stem Cells Comments Off on Home | EMBO Reports | October 17th, 2016

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Academic research council

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Acute coronary symptoms

Acute coronary syndromes

Adenoviridae and iridoviridae

Adherence hypertension treatment

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African sleeping sickness

Aids/ hiv current senario

Airborne contaminants

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Air pollution armenia

American heart association

Aminoglycosidearginine conjugates

Analytic epidemiology

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Anger regulation interventions

Antimicrobial resistance

Antimicrobrial peptides

Antiretroviral agents

Assessing disease frequency

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Attack preparedness events

Avian influenza: zoonosis

Bacterial membrane vesicles

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Bone marrow transplantation

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Supercourse: Epidemiology, the Internet, and Global Health

Cardiac Stem Cells Comments Off on Supercourse: Epidemiology, the Internet, and Global Health | October 16th, 2016

9thInternational Conference on Hematology

Date: November 02-04, 2017

Venue: Las Vegas, USA

Hematology 2016 has been designed with many interesting and informative scientific sessions; it includes all possible aspects of Hematology research.

Hematology

Erythrocytesare also known as red blood cells which carry oxygen to the body and collect carbon dioxide from the body by the use of hemoglobin and its life span of 120 days. along the side the leucocytes helps in protecting the healthy cells because the W.B.C (leucocytes) act as the defending cells in protecting the immune system from the foreign cells. Theseleucocytesare multipotent cells in bone marrow and there life span is of 3-4 days where the yellow blood cells are called as thrombocytes they are where small and irregular in shape they have life span of 5-9 days they are mostly seen in mammals they help in clotting of blood which are in fibrin form called as thrombosis these lead to heart stroke, blockage of blood in blood mostly in arms and legs. where C.B.C is known ascomplete blood countis done to know the number of cells in a body these are mainly done by lab technician presently they are been tested by automatic analyzer the high and low amount of cells will lead to many diseases. Decrease of R.B.C in the body these causes of anemia which leads to weakness, feeling of tired, shortness of breath and person will be noticeably pale. Formation of blood cellular components are called as Hematopoiesis and all the cellular blood components are derived from hematopoiesis stem cells in a healthy individual nearly 10111012new blood cells are produced these help in steady peripheral circulation. If there is a increases of R.B.C in the body these causes polycythemia these can be measured through hematocrit level.

Blood Disorders

Hemophilia Ais a genetic deficiency in clottingfactor VIII,which causes increased bleeding and usually affects males. About 70% of the time it is inherited as an X-linked recessive trait, but around 30% of cases arise from spontaneous mutations. Hemophilia B is ablood clottingdisorder caused by amutationof thefactor IXgene, leading to a deficiency of factor IX. It is the second-most common form ofhaemophilia, rarer thanhaemophilia A. It is sometimes calledChristmas disease, named afterStephen Christmas, the first patient described with this disease.In addition, the first report of its identification was published in the Christmas edition of theBritish Medical Journal.Hemophilia C is a mild form of haemophiliaaffecting both sexes. However, it predominantly occurs in Jews ofAshkenazidescent. It is the fourth most common coagulationdisorder aftervon Willebrand's diseaseandhaemophiliaAandB.In theUSAit is thought to affect 1 in 100,000 of the adult population, making it 10% as common as haemophilia A. Idiopathic thrombocytopenic purpura(ITP), also known asimmune thrombocytopenia,primary immune thrombocytopenia,primary immune thrombocytopenic purpuraorautoimmune thrombocytopenic purpura, is defined as isolated low platelet count (thrombocytopenia) with normalbone marrowand the absence of other causes of thrombocytopeniaVon Willebrand diseasesis the most common hereditarycoagulationabnormality described in humans. Platelets also called "thrombocytes" areblood cellswhose function (along with thecoagulation factors) is to stop bleeding by clumping and clogging blood vessel injuries.Platelets have nocell nucleus: Coagulation is highlyconservedthroughout biology; in allmammals, coagulation involves both a cellular (platelet) and aprotein(coagulation factor) component and these are occoured due togenetic blood disorders

Hematologic Malignancies

Lymphatic leukemiawhich effect the white blood cells(w.b.c) they are closely related to the lymphomas and some of them are unitary diseases which related to the adult T cells leukemia these come under the lymphoproliferative disorders. Mostly they involve in the B-cell sub type lymphocytes. The myeloid leukemia is preferred to the granulocyte precursor in the bone marrow and spinal cord and these arises the abnormal growth in the blood from tissues in the bone marrow. They are mainly related to the hematopoietic cells and these sub title into acute and chronic lymphoblastic leukemia. The acute leukemia is that rapidly producing immature blood cells as they are bulk number of cells healthy cells are not produced in bone marrow due this spill over the blood stream which spread to other body parts. Where as in chronic leukemia highly bulid of matured cells are formed but still abnormal white cells are formed these can not be treated immediately mostly seen in older people. The cancer which originate from white blood cells are called as lymphoma and this disorder is mainly seen inHodgkin lymphomathese diseases is treated by radiation and chemotherapy, orhematopoietic stem cell transplantation. The cancer which starts with in the cell are called as Non Hodgkin lymphocytes and these lymphocytes are of lymph nodes. The bone marrow which develops too many white blood cells leads tomultiple myleoma. The further details on malignance are been discussed inHematology oncology conference-2015.

Hematology and immunology

Blood groupsare of ABO type and but at present the Rh blood grouping of 50 well defined antigens in which 5 are more important they are D,C,c,E and e and Rh factors are of Rh positive and Rh negative which refers to the D-antigen. These D-antigen helps in prevention of erythroblast fetalis lacking of Rh antigen it defined as negative and presences of Rh antigen in blood leads to positive these leads to rh incompatibility. The prevention treatment of diseases related to the blood is called as the Hematology. The hematologists conduct works on cancer to. The disorder of immune system leading to hypersensitivity is called asClinical Immunologyand the abnormal growth of an infection are known as Inflammation and the arise of an abnormal immune response to the body or an immune suppression are known as Auto immune disorder. The stem cell therapy is used to treat or prevent a disease or a condition mostly Bone marrow stem cell therapy is seen and recently umbilical cord therapy Stem cell transplantation strategies remains a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases.

Blood Transplantation

Theumbilical cordis a conduit between the developingembryoorfetusand theplacenta. The umbilical vein supplies the fetus with nutrient-richbloodfrom theplacenta The hematopoitic bone marrow transplant, the HSC are removed from a large bone of the donor, typically thepelvis, through a largeneedlethat reaches the center of the bone. Acute myeloid leukemia is a cancerof themyeloidline of blood cells, characterized by the rapid growth of abnormalwhite blood cellsthat accumulate in thebone marrowand interfere withthe production of normal blood cells and the Thrombosis is the formation of ablood clot inside ablood vessel, obstructing the flow ofbloodthrough thecirculatory system. TheHemostaticis a process which causes bleeding to stop, meaning to keep blood within a damaged blood vessel this is the first stage of wound healing. Metabolic syndromeis a disorder of energy utilization and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions, obesity,elevated blood pressure,elevated fasting plasma glucose,high serum triglycerides, and lowhigh-density lipoprotein(HDL) levels. Metabolic syndrome increases the risk developingcardiovascular diseaseanddiabetes.

Diagnosis and Treatment

Palliative careis amultidisciplinary approachto specialisedmedical carefor people with seriousillnesses The spleen, similar in structure to a largelymph node, acts as a blood filter. Anticoagulants(antithrombics) are a class of drugs that work to prevent thecoagulation(clotting) of blood. Some anticoagulants are used in medical equipment, such astest tubes ,blood transfusionbags, andrenal dialysisequipment. Anvena cava filteris a type of vascular filter, amedicaldevice that is implanted byinterventional radiologistsor vascular surgeons into theinferior vena cavato presumably prevent life-threateningpulmonary emboliistherapyusingionizing radiation, generally as part of cancer treatmentto control or killmalignantcells. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body. The subspecialty ofoncologythat focuses on radiotherapy is calledradiation oncology. Translational research is another term fortranslated researchandtranslational science, Applying knowledge from basic science is a major stumbling block in science, partially due to the compartmentalization within science. Targeted drug delivery is a method of deliveringmedicationto a patient in a manner that increases theconcentrationof the medication in some parts of the body relative to others.

New Drug Development in Haematology

The development of antibiotic resistance in particular stems from the drugs targeting only specific bacterial molecules. Because the drugisso specific, any mutation in these molecules will interfere with or negate its destructive effect, resulting in antibiotic resistance. Known asDrug deliveryConditions treated with combination therapy includetuberculosis,leprosy,cancer,malaria, andHIV/AIDS. One major benefit of combination therapies is that they reduce development ofdrug resistance, since a pathogen or tumor is less likely to have resistance to multiple drugs simultaneously.Artemisinin-based monotherapies for malaria are explicitly discouraged to avoid the problem of developing resistance to the newer treatment. Drug Induced Blood Disorders causes of sickle cell anemia,pale skin non steroids antiinflammatory drugswhich causes ulcers Using drug repositioning, pharmaceutical companies have achieved a number successes, for examplePfizer'sViagrainerectile dysfunctionandCelgene'sthalidomidein severe erythema nodosum leprosum. Smaller companies, including Ore Pharmaceuticals,Biovista, Numedicus,Melior Discoveryand SOM Biotech are also performing drug repositioning on a systematic basis. These companies use a combination of approaches including in silico biology and in vivo/in vitro experimentation to assess a compound and develop and confirm hypotheses concerning its usage for new indications.

Hematology Research

Lymphatic diseasesthis is a type of cancer of the lymphatic system. It can start almost any where in the body. It's believed to be caused by HIV, Epstein-Barr Syndrome, age and family history. Symptoms include weight loss, fever, swollen lymph nodes, night sweats, itchy skin, fatigue, chest pain, coughing and/or trouble swallowing. Thelymphatic systemis part of thecirculatory system, comprising a network oflymphatic vesselsthat carry a clear fluid called lymph directionally towards the heart. The lymphatic system was first described in the seventeenth century independently byOlaus RudbeckandThomas Bartholin. Unlike thecardiovascular systemthe lymphatic system is not a closed system. The human circulatory system processes an average of 20 litres ofbloodper day throughcapillary filtrationwhich removesplasmawhile leaving theblood cells. Roughly 17 litres of the filtered plasma get reabsorbed directly into the blood vessels, while the remaining 3 litres are left behind in theinterstitial fluid. One of the main functions of the lymph system is to provide an accessory return route to the blood for the surplus 3 litres. Lymphatic diseases are ofNon-Hodgkin's Lymphoma, Hodgkins. Thethymusis a specialized primarylymphoidorgan of theimmune system. Within the thymus,T cellsor Tlymphocytesmature. T cells are critical to theadaptive immune system, where the body adapts specifically to foreign invaders.One of the example of lymph node development. Formation oflymph nodeinto the tumor which lead to cancer called oncology.

Various Aspects of Haematology

Pediatric Haematology and Oncologyis an internationalpeer-reviewedmedical journalthat covers all aspects ofpediatrichematologyandoncology. The journal covers immunology, pathology, and pharmacology in relation to blood diseases and cancer in children and shows how basic experimental research can contribute to the understanding of clinical problems. Physicians specialized in hematology are known ashematologistsorhaematologists. Their routine work mainly includes the care and treatment of patients with hematological diseases, although some may also work at the hematology laboratory viewingblood filmsandbone marrowslides under themicroscope, interpreting various hematological test results andblood clotting testresults. In some institutions, hematologists also manage the hematology laboratory. Physicians who work in hematology laboratories, and most commonly manage them, are pathologists specialized in the diagnosis of hematological diseases, referred to as hematopathologistsorhaematopathologists.Experimental Hematologyis apeer-reviewedmedical journalofhematology, which publishesoriginal researcharticles and reviews, as well as the abstracts of the annual proceedings of theSociety for Hematology and Stem Cells and they should be done under theHematology guidlines.

Blood Based Products

Ablood substituteis a substance used to mimic and fulfill some functions ofbiologicalblood. It aims to provide an alternative toblood transfusion, which is transferring blood orblood-based productsfrom one person into another. Thus far, there are no well-acceptedoxygen-carryingblood substitutes, which is the typical objective of ared blood celltransfusion; however, there are widely available non-bloodvolume expandersfor cases where only volume restoration is required. These are helping doctors and surgeons avoid the risks of disease transmission and immune suppression, address the chronic blood donor shortage, and address the concerns of Jehovah's Witnesses and others who have religious objections to receiving transfused blood.Pathogen reductionusing riboflavin and UV lightis a method by which infectiouspathogensinblood for transfusionare inactivated by addingriboflavinand irradiating withUV light. This method reduces the infectious levels of disease-causing agents that may be found in donated blood components, while still maintaining good quality blood components for transfusion. This type of approach to increase blood safety is also known as pathogen inactivation in the industry. Anartificial cellorminimal cellis an engineered particle that mimics one or many functions of abiological cell. The term does not refer to a specific physical entity, but rather to the idea that certain functions or structures of biological cells can be replaced or supplemented with a synthetic entity. Often, artificial cells are biological or polymeric membranes which enclose biologically active materials. As such,nanoparticles,liposomes,polymersomes, microcapsules and a number of other particles have qualified as artificial cells.Manufacturing of semi synthetic products of drugs are known as therapeutic biological products.Anticoagulants(antithrombics) are a class of drugs that work to prevent thecoagulation(clotting) of blood. Such substances occur naturally in leeches and blood-sucking insects.

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Cardiac Stem Cells Comments Off on Hematology Conferences | Blood Disorder Conferences | USA … | October 9th, 2016

The 5th International Conference on Tissue Engineering & Regenerative Medicine which is going to be held during September 12-14, 2016 at Berlin, Germany will bring together world-class personalities working on stem cells, tissue engineering and regenerative medicine to discuss materials-related strategies for disease remediation and tissue repair.

Tissue Regeneration

In the field of biology, regeneration is the progression of renewal, regeneration and growth that makes it possible for genomes, cells, organ regeneration to natural changes or events that cause damage or disturbance.This study is carried out as craniofacial tissue engineering, in-situtissue regeneration, adipose-derived stem cells for regenerative medicine which is also a breakthrough in cell culture technology. The study is not stopped with the regeneration of tissue where it is further carried out in relation with cell signaling, morphogenetic proteins. Most of the neurological disorders occurred accidental having a scope of recovery by replacement or repair of intervertebral discs repair, spinal fusion and many more advancements. The global market for tissue engineering and regeneration products such as scaffolds, tissueimplants, biomimetic materials reached $55.9 billion in 2010 and it is expected to reach $89.7 billion by 2016 at a compounded annual growth rate (CAGR) of 8.4%. It grows to $135 billion by 2024.

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5th InternationalConference on Tissue Engineering and Regenerative Medicine September 12-14, 2016 Berlin, Germany; 5th International Conference onCell and Gene Therapy May 19-21, 2016 San Antonio, USA; InternationalConference on Cancer Immunologyand ImmunotherapyJuly 28-30, 2016 Melbourne, Australia; InternationalConference on Molecular BiologyOctober 13-15, 2016 Dubai, UAE; Tissue Niches and Resident Stem Cells in Adult Epithelia Gordon Research Conference, Regulation of Tissue Homeostasis by Signalling in the Stem Cell Niche August 7-12, Hong Kong, China; 10 Years of IPSCs, Cell Symposia, September 25-27, 2016 Berkeley, CA, USA; World Stem Cells and Regenerative Medicine Congress May 18-20, 2016 London, UK; Notch Signaling in Development, Regeneration and Disease Gordon Research Conference, July 31-August 5, 2016 Lewiston, ME, USA

Designs for Tissue Engineering

The developing field of tissue engineering aims to regenerate damaged tissues by combining cells from the body withbioresorbablematerials, biodegradable hydrogel, biomimetic materials, nanostructures andnanomaterials, biomaterials and tissue implants which act as templates for tissue regeneration, to guide the growth of new tissue by using with the technologies. The global market for biomaterials, nanostructures and bioresorbable materials are estimated to reach $88.4 billion by 2017 from $44.0 billion in 2012 growing at a CAGR of 15%. Further the biomaterials market estimated to be worth more than 300 billion US Dollars and to be increasing 20% per year.

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5th International ConferenceonCell and Gene Therapy May 19-21, 2016 San Antonio, USA; International Conference on Restorative Medicine October 24-26, 2016 Chicago, USA; InternationalConference on Molecular Biology October 13-15, 2016 Dubai, UAE; 2nd International Conference on Bio-banking August 18-19, 2016 Portland, USA; ISSCR Annual Meeting 22-25 June, 2016 San Francisco, California, USA; Keystone Cardiac Development, Regeneration and Repair (Z2) April 3 7, 2016 Snowbird, Utah, USA;EMBL Hematopoietic Stem Cells: From the Embryo to the Aging Organism, June 3-5, 2016 Heidelberg, Germany; ISSCR Pluripotency: From basic science to therapeutic applications March 22-24, 2016 Kyoto, Japan

Organ Engineering

This interdisciplinary engineering has attracted much attention as a new therapeutic means that may overcome the drawbacks involved in the current artificial organs and organtransplantationthat have been also aiming at replacing lost or severely damaged tissues or organs. Tissue engineering and regenerative medicine is an exciting research area that aims at regenerative alternatives to harvested tissues for organ transplantation with soft tissues. Although significant progress has been made in thetissue engineeringfield, many challenges remain and further development in this area will require ongoing interactions and collaborations among the scientists from multiple disciplines, and in partnership with the regulatory and the funding agencies. As a result of the medical and market potential, there is significant academic and corporate interest in this technology.

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International Conference on Restorative Medicine October 24-26, 2016 Chicago, USA; 5th InternationalConference on Cell and Gene Therapy May 19-21, 2016 San Antonio, USA; 5th International Conference on Regenerative Medicine September 12-14, 2016 Berlin, Germany; 2nd International Conference on Tissue preservation August 18-19, 2016 Portland, USA;Cell and Gene TherapyJanuary 25-27, 2016 Washington D.C., USA; ISSCR Stem Cell Models of Neural Degeneration and Disease February 1-3, 2016 Dresden, Germany; Craniofacial Morphogenesis and Tissue Regeneration March 12-18, 2016 California, USA; Keystone Stem Cells and Cancer (C1) March 6-10, Colorado, USA; Keystone Stem Cells and Regeneration in the Digestive Organs (X6) March 13 17 Colorado, USA

Cancer Stem Cells

The characterization of cancer stem cell is done by identifying the cell within a tumor that possesses the capacity to self-renew and to cause theheterogeneous lineagesof cancer cells that comprise the tumor. This stem cell which acts as precursor for the cancer acts as a tool against it indulging the reconstruction of cancer stem cells, implies as the therapeutic implications and challenging the gaps globally. The global stem cell market will grow from about $5.6 billion in 2013 to nearly $10.6 billion in 2018, registering a compound annual growth rate (CAGR) of 3.6% from 2013 through 2018. The Americas is the largest region of globalstem cellmarket, with a market share of about $2.0 billion in 2013. The region is projected to increase to nearly $3.9 billion by 2018, with a CAGR of 13.9% for the period of 2013 to 2018. Europe is the second largest segment of the global stem cell market and is expected to grow at a CAGR of 13.4% reaching about $2.4 billion by 2018 from nearly $1.4 billion in 2013.

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5th InternationalConference Cell and Gene Therapy May 19-21, 2016 San Antonio, USA; International Conference on Molecular Biology October 13-15, 2016 Dubai, UAE; 5th International Conference on Tissue EngineeringSeptember 12-14, 2016 Berlin, Germany; 2nd International Conference on Tissue preservationAugust 18-19, 2016 Portland, USA; Molecular and Cellular Basis of Growth and Regeneration (A3) January 10 14, 2016 Colorado, USA; Cell and Gene TherapyJanuary 25-27, 2016 Washington D.C., USA; ISSCR Stem Cell Models of Neural Degeneration and Disease March 13 17, 2016 Dresden, Germany; Craniofacial Morphogenesis and Tissue Regeneration March 12-18, 2016 California, USA; World Stem Cells Congress May 18-20, 2016 London, UK

Bone Tissue Engineering

Tissue engineering ofmusculoskeletal tissues, particularly bone and cartilage, is a rapidly advancing field. In bone, technology has centered on bone graft substitute materials and the development of biodegradable scaffolds. Recently, tissue engineering strategies have included cell and gene therapy. The availability of growth factors and the expanding knowledge base concerning the bone regeneration with modern techniques like recombinant signaling molecules, solid free form fabrication of scaffolds, synthetic cartilage, Electrochemical deposition,spinal fusionand ossification are new generated techniques for tissue-engineering applications. The worldwide market for bone and cartilage repairs strategies is estimated about $300 million. During the last 10/15 years, the scientific community witnessed and reported the appearance of several sources of stem cells with both osteo and chondrogenic potential.

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5th International Conference on Tissue Engineering and Regenerative Medicine September 12-14, 2016 Berlin, Germany; 3rd 2nd International Conference on Tissue preservation and Bio-banking August 18-19, 2016 Portland, USA; 5th International Conference on Cell and Gene Therapy May 19-21, 2016 San Antonio, USA; International Conference on Restorative Medicine October 24-26, 2016 Chicago, USA; 10th World Biomaterials Congress May 17-22, 2016 Quebec, Canada; 2016 TERMIS-EU Conference June 28- July1, 2016 Uppsala, Sweden; 2016 TERMIS-AP Conference Tamsui Town of New Taipei City May 23-28, 2016; 2016 TERMIS-AM Conference September 3-6, 2016, San Diego, USA; Pluripotency: From basic science to therapeutic applications 22-24 March 2016 Kyoto, Japan

Scaffolds

Scaffolds are one of the three most important elements constituting the basic concept of regenerative medicine, and are included in the core technology of regenerative medicine. Every day thousands of surgical procedures are performed to replace or repair tissue that has been damaged through disease or trauma. The developing field of tissue engineering (TE) aims to regeneratedamaged tissuesby combining cells from the body with highly porous scaffold biomaterials, which act as templates for tissue regeneration, to guide the growth of new tissue. Scaffolds has a prominent role in tissue regeneration the designs, fabrication, 3D models, surface ligands and molecular architecture, nanoparticle-cell interactions and porous of thescaffoldsare been used in the field in attempts to regenerate different tissues and organs in the body. The world stem cell market was approximately 2.715 billion dollars in 2010, and with a growth rate of 16.8% annually, a market of 6.877 billion dollars will be formed in 2016. From 2017, the expected annual growth rate is 10.6%, which would expand the market to 11.38 billion dollars by 2021.

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InternationalConference on Restorative MedicineOctober 24-26, 2016 Chicago, USA; 5th InternationalConference onCell and Gene TherapyMay 19-21, 2016 San Antonio, USA; 5th InternationalConference on Regenerative MedicineSeptember 12-14, 2016 Berlin, Germany; 2ndInternational Conference on Tissue preservationAugust 18-19, 2016 Portland, USA;Cell and Gene TherapyJanuary 25-27, 2016 Washington D.C., USA; ISSCRStem Cell Modelsof Neural Degeneration and Disease February 1-3, 2016 Dresden, Germany; Craniofacial Morphogenesis andTissue RegenerationMarch 12-18, 2016 California, USA; KeystoneStem Cells and Cancer(C1) March 6-10, Colorado, USA; KeystoneStem Cells and Regenerationin the Digestive Organs (X6) March 13 17 Colorado, USA

Tissue Regeneration Technologies

Guided tissue regeneration is defined as procedures attempting to regenerate lost periodontal structures through differential tissue responses. Guidedbone regenerationtypically refers to ridge augmentation or bone regenerative procedures it typically refers to regeneration of periodontal therapy. The recent advancements and innovations in biomedical and regenerative tissue engineering techniques include the novel approach of guided tissue regeneration and combination ofnanotechnologyand regenerative medicine.

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Regeneration and Therapeutics

Regenerative medicinecan be defined as a therapeutic intervention which replaces or regenerates human cells, tissues or organs, to restore or establish normal function and deploys small molecule drugs, biologics, medical devices and cell-based therapies. It deals with the different therapeutic uses like stem cells for tissue repair, tissue injury and healing process, cardiacstem cell therapyfor regeneration, functional regenerative recovery, effects of aging on tissuerepair/regeneration, corneal regeneration & degeneration. The global market is expected to reach $25.5 billion by 2011 and will further grow to $36.1 billion by 2016 at a CAGR of 7.2%. It is expected to reach $65 billion mark by 2024.

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5th InternationalConference on Tissue Engineering and Regenerative MedicineSeptember 12-14, 2016 Berlin, Germany; 5th InternationalConference onCell and Gene TherapyMay 19-21, 2016 San Antonio, USA; InternationalConference on Cancer Immunologyand ImmunotherapyJuly 28-30, 2016 Melbourne, Australia; InternationalConference on Molecular BiologyOctober 13-15, 2016 Dubai, UAE; Tissue Niches andResident Stem Cells in Adult EpitheliaGordon Research Conference,Regulation of Tissue Homeostasisby Signalling in the Stem Cell Niche August 7-12, Hong Kong, China;10 Years of IPSCs, Cell Symposia, September 25-27, 2016 Berkeley, CA, USA; WorldStem Cells and Regenerative Medicine CongressMay 18-20, 2016 London, UK; Notch Signaling in Development,Regenerationand Disease Gordon Research Conference, July 31-August 5, 2016 Lewiston, ME, USA

Regenerative medicine

Regenerative medicine is a branch oftranslational researchin tissue engineering and molecular biology which deals with the process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function. The latest developments involve advances in cell and gene therapy and stem cell research, molecular therapy, dental and craniofacial regeneration.Regenerative medicineshave the unique ability to repair, replace and regenerate tissues and organs, affected due to some injury, disease or due to natural aging process. These medicines are capable of restoring the functionality of cells and tissues. The global regenerative medicine market will reach $ 67.6 billion by 2020 from $16.4 billion in 2013, registering a CAGR of 23.2% during forecast period (2014 - 2020). Small molecules and biologics segment holds prominent market share in the overall regenerative medicine technology market and is anticipated to grow at a CAGR of 18.9% during the forecast period.

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InternationalConference on Restorative MedicineOctober 24-26, 2016 Chicago, USA; 5th InternationalConference onCell and Gene TherapyMay 19-21, 2016 San Antonio, USA; 5th InternationalConference on Regenerative MedicineSeptember 12-14, 2016 Berlin, Germany; 2ndInternational Conference on Tissue preservationAugust 18-19, 2016 Portland, USA;Cell and Gene TherapyJanuary 25-27, 2016 Washington D.C., USA; ISSCRStem Cell Modelsof Neural Degeneration and Disease February 1-3, 2016 Dresden, Germany; Craniofacial Morphogenesis andTissue RegenerationMarch 12-18, 2016 California, USA; KeystoneStem Cells and Cancer(C1) March 6-10, Colorado, USA; KeystoneStem Cells and Regenerationin the Digestive Organs (X6) March 13 17 Colorado, USA

Applications of Tissue Engineering

The applications of tissue engineering and regenerative medicine are innumerable as they mark the replacement of medication andorgan replacement. The applications involve cell tracking andtissue imaging, cell therapy and regenerative medicine, organ harvesting, transport and transplant, the application of nanotechnology in tissue engineering and regenerative medicine and bio banking. Globally the research statistics are increasing at a vast scale and many universities and companies are conducting events on the subject regenerative medicine conference like tissue implants workshops, endodontics meetings, tissue biomarkers events, tissue repair meetings, regenerative medicine conferences, tissue engineering conference, regenerative medicine workshop, veterinary regenerative medicine, regenerative medicine symposiums, tissue regeneration conferences, regenerative medicine congress.

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5th InternationalConferenceCell and Gene TherapyMay 19-21, 2016 San Antonio, USA; InternationalConference on Restorative MedicineOctober 24-26, 2016 Chicago, USA; InternationalConference on Molecular BiologyOctober 13-15, 2016 Dubai, UAE; 2nd InternationalConference on Bio-bankingAugust 18-19, 2016 Portland, USA;ISSCR Annual Meeting22-25 June, 2016 San Francisco, California, USA; KeystoneCardiac Development, Regeneration and Repair (Z2) April 3 7, 2016 Snowbird, Utah, USA;EMBLHematopoietic Stem Cells: From the Embryo to the Aging Organism, June 3-5, 2016 Heidelberg, Germany; ISSCRPluripotency: From basic science to therapeutic applications March 22-24, 2016 Kyoto, Japan

Regenerative Medicine Market

There are strong pricing pressures from public healthcare payers globally as Governments try to reduce budget deficits. Regenerative medicine could potentially save public health bodies money by reducing the need for long-term care and reducing associated disorders, with potential benefits for the world economy as a whole.The global market fortissue engineeringand regeneration products reached $55.9 billion in 2010, is expected to reach $59.8 billion by 2011, and will further grow to $89.7 billion by 2016 at a compounded annual growth rate (CAGR) of 8.4%. It grows to $135 billion to 2024. The contribution of the European region was 43.3% of the market in 2010, a value of $24.2 billion. Themarketis expected to reach $25.5 billion by 2011 and will further grow to $36.1 billion by 2016 at a CAGR of 7.2%. It grows to $65 billion to 2024.

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5th InternationalConference on Tissue Engineeringand Regenerative MedicineSeptember 12-14, 2016 Berlin, Germany; 3rd 2nd InternationalConference on Tissue preservationand Bio-bankingAugust 18-19, 2016 Portland, USA; 5th InternationalConference on Cell and Gene TherapyMay 19-21, 2016 San Antonio, USA; InternationalConference on Restorative MedicineOctober 24-26, 2016 Chicago, USA; 10thWorld Biomaterials CongressMay 17-22, 2016 Quebec, Canada; 2016TERMIS-EU ConferenceJune 28- July1, 2016 Uppsala, Sweden; 2016TERMIS-AP ConferenceTamsui Town of New Taipei City May 23-28, 2016; 2016TERMIS-AM ConferenceSeptember 3-6, 2016, San Diego, USA;Pluripotency: From basic science to therapeutic applications22-24 March 2016 Kyoto, Japan

Regenerative Medicine Europe

Leading EU nations with strong biotech sectors such as the UK and Germany are investing heavily in regenerative medicine, seeking competitive advantage in this emerging sector. The commercial regenerative medicine sector faces governance challenges that include a lack of proven business models, an immature science base and ethical controversy surrounding hESC research. The recent global downturn has exacerbated these difficulties: private finance has all but disappeared; leading companies are close to bankruptcy, and start-ups are struggling to raise funds. In the UK the government has responded by announcing 21.5M funding for the regenerative medicine industry and partners. But the present crisis extends considerably beyond regenerative medicine alone, affecting much of the European biotech sector. A 2009 European Commission (EC) report showed the extent to which the global recession has impacted on access to VC finance in Europe: 75% of biopharma companies in Europe need capital within the next two years if they are to continue their current range of activities.

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InternationalConference on Restorative MedicineOctober 24-26, 2016 Chicago, USA; 5th InternationalConference onCell and Gene TherapyMay 19-21, 2016 San Antonio, USA; 5th InternationalConference on Regenerative MedicineSeptember 12-14, 2016 Berlin, Germany; 2ndInternational Conference on Tissue preservationAugust 18-19, 2016 Portland, USA;Cell and Gene TherapyJanuary 25-27, 2016 Washington D.C., USA; ISSCRStem Cell Modelsof Neural Degeneration and Disease February 1-3, 2016 Dresden, Germany; Craniofacial Morphogenesis andTissue RegenerationMarch 12-18, 2016 California, USA; KeystoneStem Cells and Cancer(C1) March 6-10, Colorado, USA; KeystoneStem Cells and Regenerationin the Digestive Organs (X6) March 13 17 Colorado, USA

Embryonic Stem Cell

Embryonic stem cells are pluripotent, meaning they are able to grow (i.e. differentiate) into all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body as long as they are specified to do so. Embryonic stem cells are distinguished by two distinctive properties: their pluripotency, and their ability to replicate indefinitely. ES cells are pluripotent, that is, they are able to differentiate into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm. These include each of the more than 220 cell types in the adult body. Pluripotency distinguishes embryonic stem cells from adult stem cells found in adults; while embryonic stem cells can generate all cell types in the body, adult stem cells are multipotent and can produce only a limited number of cell types. Additionally, under defined conditions, embryonic stem cells are capable of propagating themselves indefinitely. This allows embryonic stem cells to be employed as useful tools for both research and regenerative medicine, because they can produce limitless numbers of themselves for continued research or clinical use.

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5th InternationalConference on Tissue Engineering and Regenerative MedicineSeptember 12-14, 2016 Berlin, Germany; 5th InternationalConference onCell and Gene TherapyMay 19-21, 2016 San Antonio, USA; InternationalConference on Cancer Immunologyand ImmunotherapyJuly 28-30, 2016 Melbourne, Australia; InternationalConference on Molecular BiologyOctober 13-15, 2016 Dubai, UAE; Tissue Niches andResident Stem Cells in Adult EpitheliaGordon Research Conference,Regulation of Tissue Homeostasisby Signalling in the Stem Cell Niche August 7-12, Hong Kong, China;10 Years of IPSCs, Cell Symposia, September 25-27, 2016 Berkeley, CA, USA; WorldStem Cells and Regenerative Medicine CongressMay 18-20, 2016 London, UK; Notch Signaling in Development,Regenerationand Disease Gordon Research Conference, July 31-August 5, 2016 Lewiston, ME, USA

Stem Cell Transplant

Stem cell transplantation is a procedure that is most often recommended as a treatment option for people with leukemia, multiple myeloma, and some types of lymphoma. It may also be used to treat some genetic diseases that involve the blood. During a stem cell transplant diseased bone marrow (the spongy, fatty tissue found inside larger bones) is destroyed with chemotherapy and/or radiation therapy and then replaced with highly specialized stem cells that develop into healthy bone marrow. Although this procedure used to be referred to as a bone marrow transplant, today it is more commonly called a stem cell transplant because it is stem cells in the blood that are typically being transplanted, not the actual bone marrow tissue.

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5th InternationalConference Cell and Gene TherapyMay 19-21, 2016 San Antonio, USA; InternationalConference on Molecular BiologyOctober 13-15, 2016 Dubai, UAE; 5th InternationalConference on Tissue EngineeringSeptember 12-14, 2016 Berlin, Germany; 2nd InternationalConference on Tissue preservationAugust 18-19, 2016 Portland, USA; Molecular and Cellular Basis ofGrowth and Regeneration(A3) January 10 14, 2016 Colorado, USA;Cell and Gene TherapyJanuary 25-27, 2016 Washington D.C., USA; ISSCRStem Cell Modelsof Neural Degeneration and Disease March 13 17, 2016 Dresden, Germany; Craniofacial Morphogenesis andTissue RegenerationMarch 12-18, 2016 California, USA;World Stem Cells CongressMay 18-20, 2016 London, UK

Market Analysis Report:

Tissue engineering is an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ. Regenerative medicine is not one discipline. It can be defined as a therapeutic intervention which replaces or regenerates human cells, tissues or organs, to restore or establish normal function and deploys small molecule drugs, biologics, medical devices and cell-based therapies

Currently it has emerged as a rapidly diversifying field with the potential to address the worldwide organ shortage issue and comprises of tissue regeneration and organ replacement. Regenerative medicine could potentially save public health bodies money by reducing the need for long-term care and reducing associated disorders, with potential benefits for the world economy as a whole.The global tissue engineering and regeneration market reached $17 billion in 2013. This market is expected to grow to nearly $20.8 billion in 2014 and $56.9 billion in 2019, a compound annual growth rate (CAGR) of 22.3%. On the basis of geography, Europe holds the second place in the global market in the field of regenerative medicine & tissue engineering. In Europe countries like UK, France and Germany are possessing good market shares in the field of regenerative medicine and tissue engineering. Spain and Italy are the emerging market trends for tissue engineering in Europe.

Tissue engineering is "an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ. Currently it has emerged as a rapidly diversifying field with the potential to address the worldwide organ shortage issue and comprises of tissue regeneration and organ replacement. A novel set of tissue replacement parts and implementation strategies had shown a great revolution in this field. Cells placed on or within the tissue constructs is the most common methodology in tissue engineering.

Regenerative medicine is not one discipline. It can be defined as a therapeutic intervention which replaces or regenerates human cells, tissues or organs, to restore or establish normal function and deploys small molecule drugs, biologics, medical devices and cell-based therapies

This field continues to evolve. In addition to medical applications, non-therapeutic applications include using tissues as biosensors to detect biological or chemical threat agents, and tissue chips that can be used to test the toxicity of an experimental medication. Tissue Engineering and Regenerative Medicine is the major field in Medicine, which is still under research and the advancements are maximizing day to day.

Regenerative Medicine-2015 is an engrossed a vicinity of cognizant discussions on novel subjects like Tissue Regeneration, Materials & Designs for Tissue Engineering, Stem CellTools to Battle Cancer, Bioreactors in Tissue Engineering, Regeneration & Therapeutics, Cord Blood & Regenerative Medicine and Clinical Medicine, to mention a few. The three days event implants a firm relation of upcoming strategies in the field of Tissue Science & Regenerative Medicine with the scientific community. The conceptual and applicable knowledge shared, will also foster organizational collaborations to nurture scientific accelerations.We bring together business, creative, and technology leaders from the tissue engineering, marketing, and research industry for the most current and relevant.

Berlin is one of the largest and most diverse science regions in Europe. Roughly 200,000 people from around the world teach, research, work and study here. Approximately 17 percent of all students come from abroad, most of them from China, Russia and the USA. Many cooperative programs link Berlins institutes of higher education with partner institutes around the world. Berlin is a city of science at the heart of Europe a city whose history of scientific excellence stems from its many important research institutions and its long track record of scientific breakthroughs. Berlin has numerous modern Technology Centers. Their science-oriented infrastructure makes them attractive locations for young, technology-oriented companies.

Germany places great emphasis on globally networked research cooperation. Many organizations support international researchers and academics: Today more than 32,000 are being supported with scholarships. Besides this, research funding in Germany has the goal of financing the development of new ideas and technologies. The range covers everything from basic research in natural sciences, new technologies to structural research funding at institutions of higher education. On the basis of geography, the regenerative medicine bone and joint market Europe hold the second place in the global market in the field of regenerative medicine & tissue engineering. The market growth is expected to reach $65 billion by 2024 in Europe. In Europe countries like UK, France, and Germany are possessing good market share in the field of regenerative medicine and tissue engineering. Spain and Italy are the emerging market trends for tissue engineering in Europe. As per the scope and emerging market for tissue engineering and regenerative medicine Berlin has been selected as Venue for the 5th International Conference on Tissue Science and Regenerative Medicine.

Meet Your Target MarketWith members from around the world focused on learning about Advertising and marketing, this is the single best opportunity to reach the largest assemblage of participants from the tissue engineering and regenerative medicine community. The meeting engrossed a vicinity of cognizant discussions on novel subjects like Tissue Regeneration, Materials & Designs for Tissue Engineering, Stem CellTools to Battle Cancer, Bioreactors in Tissue Engineering, Regeneration & Therapeutics, Cord Blood & Regenerative Medicine and Clinical Medicine, to mention a few. The three days event implants a firm relation of upcoming strategies in the field of Tissue Engineering & Regenerative Medicine with the scientific community. The conceptual and applicable knowledge shared, will also foster organizational collaborations to nurture scientific accelerations.Conduct demonstrations, distribute information, meet with current and potential customers, make a splash with a new product line, and receive name recognition.

International Stem Cell Forum (ISCF)

International Society for Stem Cell Research (ISSCR)

UK Medical Research Council (MRC)

Australian Stem Cell Center

Canadian Institutes of Health Research (CIHR)

Euro Stem Cell (ACR)

Center for Stem Cell Biology

Stem Cell Research Singapore

UK National Stem Cell Network

Spain Mobile Marketing Association

European Marketing Confederation (EMC)

European Letterbox Marketing Association(ELMA)

European Sales & Marketing Association (ESMA)

The Incentive Marketing Association (IMA Europe)

European Marketing Academy

Figure 1: Statistical Analysis of Societies and Associations

Source: Reference7

Presidents or Vice Presidents/ Directors of Associations and Societies, CEOs of the companies associated with regenerative medicine and tissue engineering Consumer Products. Retailers, Marketing, Advertising and Promotion Agency Executives, Solution Providers (digital and mobile technology, P-O-P design, retail design, and retail execution), Professors and Students from Academia in the study of Marketing and Advertising filed.

Industry 40%

Academia 50%

Others 10%

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Cardiac Stem Cells Comments Off on Regenerative Medicine Conferences | Tissue Engineering … | October 3rd, 2016

Track-1 Cell Therapy:

Cell therapyas performed by alternativemedicinepractitioners is very different from the controlled research done by conventionalstem cellmedical researchers. Alternative practitioners refer to their form of cell therapy by several other different names includingxenotransplanttherapy,glandular therapy, and fresh cell therapy. Proponents ofcell therapyclaim that it has been used successfully to rebuild damaged cartilage in joints, repair spinal cord injuries,strengthen a weakenedimmune system, treat autoimmune diseases such as AIDS, and help patients withneurological disorderssuch as Alzheimers disease,Parkinson's diseaseand epilepsy.

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Track-2 Gene therapy:

Gene therapyand cell therapy are overlapping fields of biomedical research with the goals of repairing the direct cause of genetic diseases in the DNA orcellularpopulation, respectively. The development of suitablegene therapytreatments for manygenetic diseasesand some acquired diseases has encountered many challenges and uncovered new insights into gene interactions and regulation. Further development often involves uncovering basic scientific knowledge of the affected tissues, cells, and genes, as well as redesigning vectors, formulations, and regulatory cassettes for the genes.Cell therapyis expanding its repertoire of cell types for administration.Cell therapytreatment strategies include isolation and transfer of specific stem cell populations, administration of effector cells, and induction of mature cells to becomepluripotent cells, and reprogramming of mature cells.

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Track-3 Cell and gene therapy products:

Articles containing or consisting ofhuman cellsor tissues that are intended for implantation,transplantation, infusion, or transfer to a human recipient.Gene therapiesare novel and complex products that can offer unique challenges in product development. Hence, ongoing communication between the FDA and stakeholders is essential to meet these challenges.Gene therapy productsare being developed around the world, the FDA is engaged in a number of international harmonization activities in this area.

Examples:Musculoskeletal tissue, skin, ocular tissue, human heart valves;vascular graft, dura mater, reproductive tissue/cells, Stem/progenitor cells,somatic cells, Cells transduced withgene therapyvectors , Combination products (e.g., cells or tissue + device)

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Track-4 Cellular therapy:

Cellular therapy, also calledlive cell therapy, cellular suspensions, glandular therapy, fresh cell therapy, sick cell therapy,embryonic cell therapy, andorgan therapy- refers to various procedures in which processed tissue from animal embryos, foetuses or organs, is injected or taken orally. Products are obtained from specific organs or tissues said to correspond with the unhealthy organs or tissues of the recipient. Proponents claim that the recipient's body automatically transports the injected cells to thetarget organs, where they supposedly strengthen them and regenerate their structure. The organs and glands used in cell treatment include brain, pituitary,thyroid, adrenals, thymus, liver,kidney, pancreas, spleen, heart,ovary, testis, and parotid. Several different types of cell or cell extract can be given simultaneously - some practitioners routinely give up to 20 or more at once.

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Track-5 Cancer gene therapy:

Cancer therapiesare drugs or other substances that block the growth and spread ofcancerby interfering with specific molecules ("molecular targets") that are involved in the growth, progression, and spread ofcancer. Many cancer therapies have been approved by the Food and Drug Administration (FDA) to treat specific types of cancer. The development of targetedtherapiesrequires the identification of good targets that is, targets that play a key role in cancer cell growth and survival. One approach to identify potential targets is to compare the amounts of individualproteinsin cancer cells with those in normal cells.Proteinsthat are present in cancer cells but not normal cells or that are more abundant incancercells would be potential targets, especially if they are known to be involved incell growthor survival.

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Track-6 Nano therapy:

Nano Therapymay be defined as the monitoring, repair, construction and control of human biological systems at themolecular level, using engineerednanodevicesand nanostructures. Basic nanostructured materials, engineeredenzymes, and the many products of biotechnology will be enormously useful in near-term medical applications. However, the full promise ofnanomedicineis unlikely to arrive until after the development of precisely controlled or programmable medical Nano machines andnanorobots.

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Track-7 Skin cell therapy:

Stem cellshave newly become a huge catchphrase in theskincarebiosphere. Skincare specialists are not usingembryonic stem cells; it is impossible to integrate live materials into a skincare product. Instead, scientists are creating products with specialized peptides andenzymesor plantstem cellswhich, when applied topically on the surface, help to protect the human skinstem cellsfrom damage and deterioration or stimulate the skins own stem cells. Currently, the technique is mainly used to save the lives of patients who have third degree burns over very large areas of their bodies.

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Track-8 HIV gene therapy:

Highly activeantiretroviral therapydramatically improves survival inHIV-infected patients. However, persistence of HIV in reservoirs has necessitated lifelong treatment that can be complicated bycumulative toxicities, incomplete immune restoration, and the emergence of drug-resistant escapemutants. Cell and gene therapies offer the promise of preventing progressiveHIV infectionby interfering with HIV replication in the absence of chronicantiviral therapy.

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Track-9 Diabetes for gene therapy:

Cell therapyapproaches for this disease are focused on developing the most efficient methods for the isolation ofpancreasbeta cells or appropriatestem cells, appropriate location forcell transplant, and improvement of their survival upon infusion. Alternatively, gene andcell therapyscientists are developing methods to reprogram some of the other cells of the pancreas to secreteinsulin. Currently ongoingclinical trialsusing these gene andcell therapystrategies hold promise for improved treatments of type I diabetes in the future. The firstgene therapyapproach to diabetes was put forward shortly after the cloning of theinsulingene. It was proposed that non-insulin producing cells could be made into insulin-producingcells using a suitable promoter and insulin gene construct, and that these substitute cells could restore insulin production in type 1 and some type 2 diabetics.

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Track-10 Viral gene therapy:

Converting avirusinto a vector Theviral life cyclecan be divided into two temporally distinct phases: infection and replication. Forgene therapyto be successful, an appropriate amount of a therapeutic gene must be delivered into the target tissue without substantial toxicity. Eachviral vectorsystem is characterized by an inherent set of properties that affect its suitability for specific gene therapy applications. For some disorders, long-term expression from a relatively small proportion of cells would be sufficient (for example, genetic disorders), whereas otherpathologiesmight require high, but transient,gene expression. For example, gene therapies designed to interfere with a viral infectious process or inhibit the growth ofcancer cellsby reconstitution of inactivated tumour suppressor genes may require gene transfer into a large fraction of theabnormal cells.

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Track-11 Stem cell therapies:

Stem cells have tremendous promise to help us understand and treat a range of diseases, injuries and other health-related conditions. Their potential is evident in the use ofblood stem cellsto treat diseases of the blood, a therapy that has saved the lives of thousands of children withleukaemia; and can be seen in the use ofstem cellsfor tissue grafts to treat diseases or injury to the bone, skin and surface of the eye. Some bone, skin andcorneal(eye) injuries and diseases can be treated bygraftingor implanting tissues, and the healing process relies on stem cells within thisimplanted tissue.

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Track-12 Stem cell preservation:

The ability to preserve the cells is critical to theirclinicalapplication. It improves patient access to therapies by increasing the genetic diversity of cells available. In addition, the ability to preserve cells improves the "manufacturability" of acell therapyproduct by permitting the cells to be stored until the patient is ready for administration of the therapy, permitting inventory control of products, and improving management of staffing atcell therapyfacilities. Finally, the ability to preservecell therapiesimproves the safety of cell therapy products by extending the shelf life of a product and permitting completion of safety and quality control testing before release of the product for use. preservation permits coordination between the manufacture of the therapy and patient care regimes.

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Track-13 Stem cell products:

The globalstemcell,Stem cell productsmarket will grow from about $5.6 billion in 2013 to nearly $10.6 billion in 2018, registering a compound annual growth rate (CAGR) of 13.6% from 2013 through 2018.This trackdiscusses the implications ofstemcellresearchand commercial trends in the context of the current size and growth of thepharmaceutical market, both in global terms and analysed by the most important national markets.

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Track-14 Genetically inherited diseases:

Agenetic diseaseis any disease that is caused by an abnormality in an individual'sgenome, the person's entiregeneticmakeup. The abnormality can range from minuscule to major -- from a discrete mutation in a single base in the DNA of a single gene to a grosschromosome abnormalityinvolving the addition or subtraction of an entirechromosomeor set of chromosomes.Most genetic diseases are the direct result of a mutation in one gene. However, one of the most difficult problems ahead is to find out how genes contribute to diseases that have a complex pattern ofinheritance, such as in the cases of diabetes,asthma,cancerandmental illness. In all these cases, no one gene has the yes/no power to say whether a person has a disease or not. It is likely that more than one mutation is required before the disease is manifest, and a number of genes may each make a subtle contribution to a person's susceptibility to a disease; genes may also affect how a person reacts toenvironmental factors.

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Track-15 Plant stem cells:

Plantshave emerged as powerful production platforms for the expression of fully functional recombinantmammalian proteins. These expression systems have demonstrated the ability to produce complexglycoproteinsin a cost-efficient manner at large scale. The full realization of thetherapeuticpotential of stem cells has only recently come into the forefront ofregenerative medicine. Stem cells are unprogrammed cells that can differentiate into cells with specific functions.Regenerative therapiesare used to stimulate healing and might be used in the future to treat various kinds of diseases.Regenerative medicinewill result in an extended healthy life span. A fresh apple is a symbol for beautiful skin. Hair greying for example could be shown to result from the fact that themelanocyte stem cellsin the hair follicle have died off.

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Track-16 Plant stem cell rejuvenation:

Asplantscannot escape from danger by running or taking flight, they need a special mechanism to withstandenvironmental stress. What empowers them to withstand harsh attacks and preserve life is the stem cell. According to Wikipedia, plantstem cellsnever undergo theagingprocess but constantly create new specialized and unspecialized cells, and they have the potential to grow into any organ, tissue, or cell in the body. The everlasting life is due to the hormones auxin andgibberellin. British scientists found that plant stem cells were much more sensitive toDNAdamage than other cells. And once they sense damage, they trigger death of these cells.

Rejuvenate with Plant Stem Cells

Detoxifyand release toxins on a cellular level. Nourishyour body with vital nutrients. Regenerateyour cells and diminish the effects of aging.

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Track-17 Clinical trials in cell and gene therapy:

Aclinical trialis a research study that seeks to determine if a treatment is safe and effective. Advancing new cell andgene therapies(CGTs) from the laboratory into early-phaseclinical trialshas proven to be a complex task even for experienced investigators. Due to the wide variety ofCGTproducts and their potential applications, a case-by-case assessment is warranted for the design of each clinical trial.

Objectives:Determine thepharmacokineticsof this regimen by the persistence of modified T cells in the blood of these patients, Evaluate theimmunogenicityof murine sequences in chimeric anti-CEA Ig TCR, Assess immunologic parameters which correlate with the efficacy of this regimen in these patients, Evaluate, in a preliminary manner, the efficacy of this regimen in patients with CEA bearingtumours.

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Track-18 Molecular epigenetics:

Epigeneticsis the study of heritable changes in thephenotypeof a cell or organism that are not caused by its genotype. The molecular basis of anepigeneticprofile arises from covalent modifications of protein andDNAcomponents ofchromatin. The epigenetic profile of a cell often dictates cell fate, as well as mammalian development,agingand disease. Epigenetics has evolved to become the science that explains how the differences in the patterns ofgene expressionin diverse cells or tissues are executed and inherited.

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Track-19 Bioengineering therapeutics:

The goals ofbioengineeringstrategies for targetedcancertherapies are (1) to deliver a high dose of an anticancer drug directly to a cancer tumour, (2) to enhance drug uptake by malignant cells, and (3) to minimize drug uptake by non-malignant cells. In ESRD micro electro mechanical systems andnanotechnologyto create components such as robust silicon Nano pore filters that mimic natural kidney structure for high-efficiency toxin clearance. It also usestissue engineeringto build a miniature bioreactor in which immune-isolated human-derived renal cells perform key functions, such as reabsorption of water and salts.In drug delivery for a leading cause ofblindness, photo-etching fabrication techniques from themicrochipindustry to create thin-film and planar micro devices (dimensions in millionths of meters) with protectivemedicationreservoirs andnanopores(measured in billionths of meters) for insertion in the back of the eye to deliver sustained doses of drug across protective retinalepithelial tissuesover the course of several months.

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Track-20 Advanced gene therapy:

Advanced therapiesare different fromconventional medicines, which are made from chemicals or proteins.Gene-therapymedicines:these contain genes that lead to atherapeuticeffect. They work by inserting 'recombinant' genes into cells, usually to treat a variety of diseases, including genetic disorders, cancer or long-term diseases.Somatic-cell therapymedicines:these contain cells or tissues that have been manipulated to change their biological characteristics.Advanced Cell &Gene Therapyprovides guidanceinprocess development, GMP/GTP manufacturing,regulatory affairs, due diligence and strategy, specializing in cell therapy,gene therapy, and tissue-engineeredregenerative medicineproducts.

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Cell Therapy Conferences | Spain | Worldwide Events ...

Cardiac Stem Cells Comments Off on Cell Therapy Conferences | Spain | Worldwide Events … | September 23rd, 2016

Muscle is a soft tissue found in most animals. Muscle cells contain protein filaments of actin and myosin that slide past one another, producing a contraction that changes both the length and the shape of the cell. Muscles function to produce force and motion. They are primarily responsible for maintaining and changing posture, locomotion, as well as movement of internal organs, such as the contraction of the heart and the movement of food through the digestive system via peristalsis.

Muscle tissues are derived from the mesodermal layer of embryonic germ cells in a process known as myogenesis. There are three types of muscle, skeletal or striated, cardiac, and smooth. Muscle action can be classified as being either voluntary or involuntary. Cardiac and smooth muscles contract without conscious thought and are termed involuntary, whereas the skeletal muscles contract upon command.[1] Skeletal muscles in turn can be divided into fast and slow twitch fibers.

Muscles are predominantly powered by the oxidation of fats and carbohydrates, but anaerobic chemical reactions are also used, particularly by fast twitch fibers. These chemical reactions produce adenosine triphosphate (ATP) molecules that are used to power the movement of the myosin heads.[2]

The term muscle is derived from the Latin musculus meaning "little mouse" perhaps because of the shape of certain muscles or because contracting muscles look like mice moving under the skin.[3][4]

The anatomy of muscles includes gross anatomy, which comprises all the muscles of an organism, and microanatomy, which comprises the structures of a single muscle.

Muscle tissue is a soft tissue, and is one of the four fundamental types of tissue present in animals. There are three types of muscle tissue recognized in vertebrates:

Cardiac and skeletal muscles are "striated" in that they contain sarcomeres that are packed into highly regular arrangements of bundles; the myofibrils of smooth muscle cells are not arranged in sarcomeres and so are not striated. While the sarcomeres in skeletal muscles are arranged in regular, parallel bundles, cardiac muscle sarcomeres connect at branching, irregular angles (called intercalated discs). Striated muscle contracts and relaxes in short, intense bursts, whereas smooth muscle sustains longer or even near-permanent contractions.

Skeletal (voluntary) muscle is further divided into two broad types: slow twitch and fast twitch:

The density of mammalian skeletal muscle tissue is about 1.06kg/liter.[8] This can be contrasted with the density of adipose tissue (fat), which is 0.9196kg/liter.[9] This makes muscle tissue approximately 15% denser than fat tissue.

All muscles are derived from paraxial mesoderm. The paraxial mesoderm is divided along the embryo's length into somites, corresponding to the segmentation of the body (most obviously seen in the vertebral column.[10] Each somite has 3 divisions, sclerotome (which forms vertebrae), dermatome (which forms skin), and myotome (which forms muscle). The myotome is divided into two sections, the epimere and hypomere, which form epaxial and hypaxial muscles, respectively. The only epaxial muscles in humans are the erector spinae and small intervertebral muscles, and are innervated by the dorsal rami of the spinal nerves. All other muscles, including those of the limbs are hypaxial, and inervated by the ventral rami of the spinal nerves.[10]

During development, myoblasts (muscle progenitor cells) either remain in the somite to form muscles associated with the vertebral column or migrate out into the body to form all other muscles. Myoblast migration is preceded by the formation of connective tissue frameworks, usually formed from the somatic lateral plate mesoderm. Myoblasts follow chemical signals to the appropriate locations, where they fuse into elongate skeletal muscle cells.[10]

Skeletal muscles are sheathed by a tough layer of connective tissue called the epimysium. The epimysium anchors muscle tissue to tendons at each end, where the epimysium becomes thicker and collagenous. It also protects muscles from friction against other muscles and bones. Within the epimysium are multiple bundles called fascicles, each of which contains 10 to 100 or more muscle fibers collectively sheathed by a perimysium. Besides surrounding each fascicle, the perimysium is a pathway for nerves and the flow of blood within the muscle. The threadlike muscle fibers are the individual muscle cells (myocytes), and each cell is encased within its own endomysium of collagen fibers. Thus, the overall muscle consists of fibers (cells) that are bundled into fascicles, which are themselves grouped together to form muscles. At each level of bundling, a collagenous membrane surrounds the bundle, and these membranes support muscle function both by resisting passive stretching of the tissue and by distributing forces applied to the muscle.[11] Scattered throughout the muscles are muscle spindles that provide sensory feedback information to the central nervous system. (This grouping structure is analogous to the organization of nerves which uses epineurium, perineurium, and endoneurium).

This same bundles-within-bundles structure is replicated within the muscle cells. Within the cells of the muscle are myofibrils, which themselves are bundles of protein filaments. The term "myofibril" should not be confused with "myofiber", which is a simply another name for a muscle cell. Myofibrils are complex strands of several kinds of protein filaments organized together into repeating units called sarcomeres. The striated appearance of both skeletal and cardiac muscle results from the regular pattern of sarcomeres within their cells. Although both of these types of muscle contain sarcomeres, the fibers in cardiac muscle are typically branched to form a network. Cardiac muscle fibers are interconnected by intercalated discs,[12] giving that tissue the appearance of a syncytium.

The filaments in a sarcomere are composed of actin and myosin.

The gross anatomy of a muscle is the most important indicator of its role in the body. There is an important distinction seen between pennate muscles and other muscles. In most muscles, all the fibers are oriented in the same direction, running in a line from the origin to the insertion. However, In pennate muscles, the individual fibers are oriented at an angle relative to the line of action, attaching to the origin and insertion tendons at each end. Because the contracting fibers are pulling at an angle to the overall action of the muscle, the change in length is smaller, but this same orientation allows for more fibers (thus more force) in a muscle of a given size. Pennate muscles are usually found where their length change is less important than maximum force, such as the rectus femoris.

Skeletal muscle is arranged in discrete muscles, an example of which is the biceps brachii (biceps). The tough, fibrous epimysium of skeletal muscle is both connected to and continuous with the tendons. In turn, the tendons connect to the periosteum layer surrounding the bones, permitting the transfer of force from the muscles to the skeleton. Together, these fibrous layers, along with tendons and ligaments, constitute the deep fascia of the body.

The muscular system consists of all the muscles present in a single body. There are approximately 650 skeletal muscles in the human body,[13] but an exact number is difficult to define. The difficulty lies partly in the fact that different sources group the muscles differently and partly in that some muscles, such as palmaris longus, are not always present.

A muscular slip is a narrow length of muscle that acts to augment a larger muscle or muscles.

The muscular system is one component of the musculoskeletal system, which includes not only the muscles but also the bones, joints, tendons, and other structures that permit movement.

The three types of muscle (skeletal, cardiac and smooth) have significant differences. However, all three use the movement of actin against myosin to create contraction. In skeletal muscle, contraction is stimulated by electrical impulses transmitted by the nerves, the motoneurons (motor nerves) in particular. Cardiac and smooth muscle contractions are stimulated by internal pacemaker cells which regularly contract, and propagate contractions to other muscle cells they are in contact with. All skeletal muscle and many smooth muscle contractions are facilitated by the neurotransmitter acetylcholine.

The action a muscle generates is determined by the origin and insertion locations. The cross-sectional area of a muscle (rather than volume or length) determines the amount of force it can generate by defining the number of sarcomeres which can operate in parallel.[citation needed] The amount of force applied to the external environment is determined by lever mechanics, specifically the ratio of in-lever to out-lever. For example, moving the insertion point of the biceps more distally on the radius (farther from the joint of rotation) would increase the force generated during flexion (and, as a result, the maximum weight lifted in this movement), but decrease the maximum speed of flexion. Moving the insertion point proximally (closer to the joint of rotation) would result in decreased force but increased velocity. This can be most easily seen by comparing the limb of a mole to a horse - in the former, the insertion point is positioned to maximize force (for digging), while in the latter, the insertion point is positioned to maximize speed (for running).

Muscular activity accounts for much of the body's energy consumption. All muscle cells produce adenosine triphosphate (ATP) molecules which are used to power the movement of the myosin heads. Muscles have a short-term store of energy in the form of creatine phosphate which is generated from ATP and can regenerate ATP when needed with creatine kinase. Muscles also keep a storage form of glucose in the form of glycogen. Glycogen can be rapidly converted to glucose when energy is required for sustained, powerful contractions. Within the voluntary skeletal muscles, the glucose molecule can be metabolized anaerobically in a process called glycolysis which produces two ATP and two lactic acid molecules in the process (note that in aerobic conditions, lactate is not formed; instead pyruvate is formed and transmitted through the citric acid cycle). Muscle cells also contain globules of fat, which are used for energy during aerobic exercise. The aerobic energy systems take longer to produce the ATP and reach peak efficiency, and requires many more biochemical steps, but produces significantly more ATP than anaerobic glycolysis. Cardiac muscle on the other hand, can readily consume any of the three macronutrients (protein, glucose and fat) aerobically without a 'warm up' period and always extracts the maximum ATP yield from any molecule involved. The heart, liver and red blood cells will also consume lactic acid produced and excreted by skeletal muscles during exercise.

At rest, skeletal muscle consumes 54.4 kJ/kg(13.0kcal/kg) per day. This is larger than adipose tissue (fat) at 18.8kJ/kg (4.5kcal/kg), and bone at 9.6kJ/kg (2.3kcal/kg).[14]

The efferent leg of the peripheral nervous system is responsible for conveying commands to the muscles and glands, and is ultimately responsible for voluntary movement. Nerves move muscles in response to voluntary and autonomic (involuntary) signals from the brain. Deep muscles, superficial muscles, muscles of the face and internal muscles all correspond with dedicated regions in the primary motor cortex of the brain, directly anterior to the central sulcus that divides the frontal and parietal lobes.

In addition, muscles react to reflexive nerve stimuli that do not always send signals all the way to the brain. In this case, the signal from the afferent fiber does not reach the brain, but produces the reflexive movement by direct connections with the efferent nerves in the spine. However, the majority of muscle activity is volitional, and the result of complex interactions between various areas of the brain.

Nerves that control skeletal muscles in mammals correspond with neuron groups along the primary motor cortex of the brain's cerebral cortex. Commands are routed though the basal ganglia and are modified by input from the cerebellum before being relayed through the pyramidal tract to the spinal cord and from there to the motor end plate at the muscles. Along the way, feedback, such as that of the extrapyramidal system contribute signals to influence muscle tone and response.

Deeper muscles such as those involved in posture often are controlled from nuclei in the brain stem and basal ganglia.

The afferent leg of the peripheral nervous system is responsible for conveying sensory information to the brain, primarily from the sense organs like the skin. In the muscles, the muscle spindles convey information about the degree of muscle length and stretch to the central nervous system to assist in maintaining posture and joint position. The sense of where our bodies are in space is called proprioception, the perception of body awareness. More easily demonstrated than explained, proprioception is the "unconscious" awareness of where the various regions of the body are located at any one time. This can be demonstrated by anyone closing their eyes and waving their hand around. Assuming proper proprioceptive function, at no time will the person lose awareness of where the hand actually is, even though it is not being detected by any of the other senses.

Several areas in the brain coordinate movement and position with the feedback information gained from proprioception. The cerebellum and red nucleus in particular continuously sample position against movement and make minor corrections to assure smooth motion.

The efficiency of human muscle has been measured (in the context of rowing and cycling) at 18% to 26%. The efficiency is defined as the ratio of mechanical work output to the total metabolic cost, as can be calculated from oxygen consumption. This low efficiency is the result of about 40% efficiency of generating ATP from food energy, losses in converting energy from ATP into mechanical work inside the muscle, and mechanical losses inside the body. The latter two losses are dependent on the type of exercise and the type of muscle fibers being used (fast-twitch or slow-twitch). For an overall efficiency of 20 percent, one watt of mechanical power is equivalent to 4.3 kcal per hour. For example, one manufacturer of rowing equipment calibrates its rowing ergometer to count burned calories as equal to four times the actual mechanical work, plus 300 kcal per hour,[15] this amounts to about 20 percent efficiency at 250 watts of mechanical output. The mechanical energy output of a cyclic contraction can depend upon many factors, including activation timing, muscle strain trajectory, and rates of force rise & decay. These can be synthesized experimentally using work loop analysis.

A display of "strength" (e.g. lifting a weight) is a result of three factors that overlap: physiological strength (muscle size, cross sectional area, available crossbridging, responses to training), neurological strength (how strong or weak is the signal that tells the muscle to contract), and mechanical strength (muscle's force angle on the lever, moment arm length, joint capabilities).

Vertebrate muscle typically produces approximately 2533N (5.67.4lbf) of force per square centimeter of muscle cross-sectional area when isometric and at optimal length.[16] Some invertebrate muscles, such as in crab claws, have much longer sarcomeres than vertebrates, resulting in many more sites for actin and myosin to bind and thus much greater force per square centimeter at the cost of much slower speed. The force generated by a contraction can be measured non-invasively using either mechanomyography or phonomyography, be measured in vivo using tendon strain (if a prominent tendon is present), or be measured directly using more invasive methods.

The strength of any given muscle, in terms of force exerted on the skeleton, depends upon length, shortening speed, cross sectional area, pennation, sarcomere length, myosin isoforms, and neural activation of motor units. Significant reductions in muscle strength can indicate underlying pathology, with the chart at right used as a guide.

Since three factors affect muscular strength simultaneously and muscles never work individually, it is misleading to compare strength in individual muscles, and state that one is the "strongest". But below are several muscles whose strength is noteworthy for different reasons.

Humans are genetically predisposed with a larger percentage of one type of muscle group over another. An individual born with a greater percentage of Type I muscle fibers would theoretically be more suited to endurance events, such as triathlons, distance running, and long cycling events, whereas a human born with a greater percentage of Type II muscle fibers would be more likely to excel at sprinting events such as 100 meter dash.[citation needed]

Exercise is often recommended as a means of improving motor skills, fitness, muscle and bone strength, and joint function. Exercise has several effects upon muscles, connective tissue, bone, and the nerves that stimulate the muscles. One such effect is muscle hypertrophy, an increase in size. This is used in bodybuilding.

Various exercises require a predominance of certain muscle fiber utilization over another. Aerobic exercise involves long, low levels of exertion in which the muscles are used at well below their maximal contraction strength for long periods of time (the most classic example being the marathon). Aerobic events, which rely primarily on the aerobic (with oxygen) system, use a higher percentage of Type I (or slow-twitch) muscle fibers, consume a mixture of fat, protein and carbohydrates for energy, consume large amounts of oxygen and produce little lactic acid. Anaerobic exercise involves short bursts of higher intensity contractions at a much greater percentage of their maximum contraction strength. Examples of anaerobic exercise include sprinting and weight lifting. The anaerobic energy delivery system uses predominantly Type II or fast-twitch muscle fibers, relies mainly on ATP or glucose for fuel, consumes relatively little oxygen, protein and fat, produces large amounts of lactic acid and can not be sustained for as long a period as aerobic exercise. Many exercises are partially aerobic and partially anaerobic; for example, soccer and rock climbing involve a combination of both.

The presence of lactic acid has an inhibitory effect on ATP generation within the muscle; though not producing fatigue, it can inhibit or even stop performance if the intracellular concentration becomes too high. However, long-term training causes neovascularization within the muscle, increasing the ability to move waste products out of the muscles and maintain contraction. Once moved out of muscles with high concentrations within the sarcomere, lactic acid can be used by other muscles or body tissues as a source of energy, or transported to the liver where it is converted back to pyruvate. In addition to increasing the level of lactic acid, strenuous exercise causes the loss of potassium ions in muscle and causing an increase in potassium ion concentrations close to the muscle fibres, in the interstitium. Acidification by lactic acid may allow recovery of force so that acidosis may protect against fatigue rather than being a cause of fatigue.[18]

Delayed onset muscle soreness is pain or discomfort that may be felt one to three days after exercising and generally subsides two to three days later. Once thought to be caused by lactic acid build-up, a more recent theory is that it is caused by tiny tears in the muscle fibers caused by eccentric contraction, or unaccustomed training levels. Since lactic acid disperses fairly rapidly, it could not explain pain experienced days after exercise.[19]

Independent of strength and performance measures, muscles can be induced to grow larger by a number of factors, including hormone signaling, developmental factors, strength training, and disease. Contrary to popular belief, the number of muscle fibres cannot be increased through exercise. Instead, muscles grow larger through a combination of muscle cell growth as new protein filaments are added along with additional mass provided by undifferentiated satellite cells alongside the existing muscle cells.[13]

Biological factors such as age and hormone levels can affect muscle hypertrophy. During puberty in males, hypertrophy occurs at an accelerated rate as the levels of growth-stimulating hormones produced by the body increase. Natural hypertrophy normally stops at full growth in the late teens. As testosterone is one of the body's major growth hormones, on average, men find hypertrophy much easier to achieve than women. Taking additional testosterone or other anabolic steroids will increase muscular hypertrophy.

Muscular, spinal and neural factors all affect muscle building. Sometimes a person may notice an increase in strength in a given muscle even though only its opposite has been subject to exercise, such as when a bodybuilder finds her left biceps stronger after completing a regimen focusing only on the right biceps. This phenomenon is called cross education.[citation needed]

Inactivity and starvation in mammals lead to atrophy of skeletal muscle, a decrease in muscle mass that may be accompanied by a smaller number and size of the muscle cells as well as lower protein content.[20] Muscle atrophy may also result from the natural aging process or from disease.

In humans, prolonged periods of immobilization, as in the cases of bed rest or astronauts flying in space, are known to result in muscle weakening and atrophy. Atrophy is of particular interest to the manned spaceflight community, because the weightlessness experienced in spaceflight results is a loss of as much as 30% of mass in some muscles.[21][22] Such consequences are also noted in small hibernating mammals like the golden-mantled ground squirrels and brown bats.[23]

During aging, there is a gradual decrease in the ability to maintain skeletal muscle function and mass, known as sarcopenia. The exact cause of sarcopenia is unknown, but it may be due to a combination of the gradual failure in the "satellite cells" that help to regenerate skeletal muscle fibers, and a decrease in sensitivity to or the availability of critical secreted growth factors that are necessary to maintain muscle mass and satellite cell survival. Sarcopenia is a normal aspect of aging, and is not actually a disease state yet can be linked to many injuries in the elderly population as well as decreasing quality of life.[24]

There are also many diseases and conditions that cause muscle atrophy. Examples include cancer and AIDS, which induce a body wasting syndrome called cachexia. Other syndromes or conditions that can induce skeletal muscle atrophy are congestive heart disease and some diseases of the liver.

Neuromuscular diseases are those that affect the muscles and/or their nervous control. In general, problems with nervous control can cause spasticity or paralysis, depending on the location and nature of the problem. A large proportion of neurological disorders, ranging from cerebrovascular accident (stroke) and Parkinson's disease to CreutzfeldtJakob disease, can lead to problems with movement or motor coordination.

Symptoms of muscle diseases may include weakness, spasticity, myoclonus and myalgia. Diagnostic procedures that may reveal muscular disorders include testing creatine kinase levels in the blood and electromyography (measuring electrical activity in muscles). In some cases, muscle biopsy may be done to identify a myopathy, as well as genetic testing to identify DNA abnormalities associated with specific myopathies and dystrophies.

A non-invasive elastography technique that measures muscle noise is undergoing experimentation to provide a way of monitoring neuromuscular disease. The sound produced by a muscle comes from the shortening of actomyosin filaments along the axis of the muscle. During contraction, the muscle shortens along its longitudinal axis and expands across the transverse axis, producing vibrations at the surface.[25]

The evolutionary origin of muscle cells in metazoans is a highly debated topic. In one line of thought scientists have believed that muscle cells evolved once and thus all animals with muscles cells have a single common ancestor. In the other line of thought, scientists believe muscles cells evolved more than once and any morphological or structural similarities are due to convergent evolution and genes that predate the evolution of muscle and even the mesoderm - the germ layer from which many scientists believe true muscle cells derive.

Schmid and Seipel argue that the origin of muscle cells is a monophyletic trait that occurred concurrently with the development of the digestive and nervous systems of all animals and that this origin can be traced to a single metazoan ancestor in which muscle cells are present. They argue that molecular and morphological similarities between the muscles cells in cnidaria and ctenophora are similar enough to those of bilaterians that there would be one ancestor in metazoans from which muscle cells derive. In this case, Schmid and Seipel argue that the last common ancestor of bilateria, ctenophora, and cnidaria was a triploblast or an organism with three germ layers and that diploblasty, meaning an organism with two germ layers, evolved secondarily due to their observation of the lack of mesoderm or muscle found in most cnidarians and ctenophores. By comparing the morphology of cnidarians and ctenophores to bilaterians, Schmid and Seipel were able to conclude that there were myoblast-like structures in the tentacles and gut of some species of cnidarians and in the tentacles of ctenophores. Since this is a structure unique to muscle cells, these scientists determined based on the data collected by their peers that this is a marker for striated muscles similar to that observed in bilaterians. The authors also remark that the muscle cells found in cnidarians and ctenophores are often contests due to the origin of these muscle cells being the ectoderm rather than the mesoderm or mesendoderm. The origin of true muscles cells is argued by others to be the endoderm portion of the mesoderm and the endoderm. However, Schmid and Seipel counter this skepticism about whether or not the muscle cells found in ctenophores and cnidarians are true muscle cells by considering that cnidarians develop through a medusa stage and polyp stage. They observe that in the hydrozoan medusa stage there is a layer of cells that separate from the distal side of the ectoderm to form the striated muscle cells in a way that seems similar to that of the mesoderm and call this third separated layer of cells the ectocodon. They also argue that not all muscle cells are derived from the mesendoderm in bilaterians with key examples being that in both the eye muscles of vertebrates and the muscles of spiralians these cells derive from the ectodermal mesoderm rather than the endodermal mesoderm. Furthermore, Schmid and Seipel argue that since myogenesis does occur in cnidarians with the help of molecular regulatory elements found in the specification of muscles cells in bilaterians that there is evidence for a single origin for striated muscle.[26]

In contrast to this argument for a single origin of muscle cells, Steinmetz et al. argue that molecular markers such as the myosin II protein used to determine this single origin of striated muscle actually predate the formation of muscle cells. This author uses an example of the contractile elements present in the porifera or sponges that do truly lack this striated muscle containing this protein. Furthermore, Steinmetz et al. present evidence for a polyphyletic origin of striated muscle cell development through their analysis of morphological and molecular markers that are present in bilaterians and absent in cnidarians, ctenophores, and bilaterians. Steimetz et al. showed that the traditional morphological and regulatory markers such as actin, the ability to couple myosin side chains phosphorylation to higher concentrations of the positive concentrations of calcium, and other MyHC elements are present in all metazoans not just the organisms that have been shown to have muscle cells. Thus, the usage of any of these structural or regulatory elements in determining whether or not the muscle cells of the cnidarians and ctenophores are similar enough to the muscle cells of the bilaterians to confirm a single lineage is questionable according to Steinmetz et al. Furthermore, Steinmetz et al. explain that the orthologues of the MyHc genes that have been used to hypothesize the origin of striated muscle occurred through a gene duplication event that predates the first true muscle cells (meaning striated muscle), and they show that the MyHc genes are present in the sponges that have contractile elements but no true muscle cells. Furthermore, Steinmetz et all showed that the localization of this duplicated set of genes that serve both the function of facilitating the formation of striated muscle genes and cell regulation and movement genes were already separated into striated myhc and non-muscle myhc. This separation of the duplicated set of genes is shown through the localization of the striated myhc to the contractile vacuole in sponges while the non-muscle myhc was more diffusely expressed during developmental cell shape and change. Steinmetz et al. found a similar pattern of localization in cnidarians with except with the cnidarian N. vectensis having this striated muscle marker present in the smooth muscle of the digestive track. Thus, Steinmetz et al. argue that the pleisiomorphic trait of the separated orthologues of myhc cannot be used to determine the monophylogeny of muscle, and additionally argue that the presence of a striated muscle marker in the smooth muscle of this cnidarian shows a fundamentally different mechanism of muscle cell development and structure in cnidarians.[27]

Steinmetz et al. continue to argue for multiple origins of striated muscle in the metazoans by explaining that a key set of genes used to form the troponin complex for muscle regulation and formation in bilaterians is missing from the cnidarians and ctenophores, and of 47 structural and regulatory proteins observed, Steinmetz et al. were not able to find even on unique striated muscle cell protein that was expressed in both cnidarians and bilaterians. Furthermore, the Z-disc seemed to have evolved differently even within bilaterians and there is a great deal diversity of proteins developed even between this clade, showing a large degree of radiation for muscle cells. Through this divergence of the Z-disc, Steimetz et al. argue that there are only four common protein components that were present in all bilaterians muscle ancestors and that of these for necessary Z-disc components only an actin protein that they have already argued is an uninformative marker through its pleisiomorphic state is present in cnidarians. Through further molecular marker testing, Steinmetz et al. observe that non-bilaterians lack many regulatory and structural components necessary for bilaterians muscle formation and do not find any unique set of proteins to both bilaterians and cnidarians and ctenophores that are not present in earlier, more primitive animals such as the sponges and amoebozoans. Through this analysis the authors conclude that due to the lack of elements that bilaterians muscles are dependent on for structure and usage, nonbilaterian muscles must be of a different origin with a different set regulatory and structural proteins.[27]

In another take on the argument, Andrikou and Arnone use the newly available data on gene regulatory networks to look at how the hierarchy of genes and morphogens and other mechanism of tissue specification diverge and are similar among early deuterostomes and protostomes. By understanding not only what genes are present in all bilaterians but also the time and place of deployment of these genes, Andrikou and Arnone discuss a deeper understanding of the evolution of myogenesis.[28]

In their paper Andrikou and Arnone argue that to truly understand the evolution of muscle cells the function of transcriptional regulators must be understood in the context of other external and internal interactions. Through their analysis, Andrikou and Arnone found that there were conserved orthologues of the gene regulatory network in both invertebrate bilaterians and in cnidarians. They argue that having this common, general regulatory circuit allowed for a high degree of divergence from a single well functioning network. Andrikou and Arnone found that the orthologues of genes found in vertebrates had been changed through different types of structural mutations in the invertebrate deuterostomes and protostomes, and they argue that these structural changes in the genes allowed for a large divergence of muscle function and muscle formation in these species. Andrikou and Arnone were able to recognize not only any difference due to mutation in the genes found in vertebrates and invertebrates but also the integration of species specific genes that could also cause divergence from the original gene regulatory network function. Thus, although a common muscle patterning system has been determined, they argue that this could be due to a more ancestral gene regulatory network being coopted several times across lineages with additional genes and mutations causing very divergent development of muscles. Thus it seems that myogenic patterning framework may be an ancestral trait. However, Andrikou and Arnone explain that the basic muscle patterning structure must also be considered in combination with the cis regulatory elements present at different times during development. In contrast with the high level of gene family apparatuses structure, Andrikou and Arnone found that the cis regulatory elements were not well conserved both in time and place in the network which could show a large degree of divergence in the formation of muscle cells. Through this analysis, it seems that the myogenic GRN is an ancestral GRN with actual changes in myogenic function and structure possibly being linked to later coopts of genes at different times and places.[28]

Evolutionarily, specialized forms of skeletal and cardiac muscles predated the divergence of the vertebrate/arthropod evolutionary line.[29][dead link] This indicates that these types of muscle developed in a common ancestor sometime before 700 million years ago (mya). Vertebrate smooth muscle was found to have evolved independently from the skeletal and cardiac muscle types.

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Muscle - Wikipedia, the free encyclopedia

Cardiac Stem Cells Comments Off on Muscle – Wikipedia, the free encyclopedia | September 22nd, 2016

For years, pediatric cardiologists have been trying to understand the origin of a puzzling structural defect of the heart muscle wall, a congenital problem called left ventricular non-compaction(LVNC). In people with this defect, the muscle of the hearts biggest pumping chamber looks spongy rather than smooth and solid.

For such congenital cardiomyopathies, currently there is no effective therapy, and the only cure is heart transplantation, said StanfordsJoseph Wu, MD, PhD, a cardiologist who led a new study of the condition that published online this week inNature Cell Biology.

His team was looking for a new way to address a very old research problem: They didnt know how much they could trust studies done on animal models of the disease. Mouse and rat models of LVNC also have spongy heart muscle, but its not clear if their defect starts the same way as in humans, nor whether findings from rodent studies could help treat humans.

So Wus team used innovative stem cell techniques instead. They took skin and blood cells donated by four members of a family affected by LVNC and converted them into induced pluripotent stem cells, which are stem cells made in a lab from adult cells. Using these stem cells, the researchers then made human heart muscle cells that they could study in a dish. That gave them a way to study what was happening in patients hearts without taking heart muscle biopsies.

Before starting their work, the researchers already knew that LVNC begins long before birth, when the heart muscle fails to make an important developmental shift. In the earliest stages of cardiac development, its normal for the muscle to be spongy. At about 8 weeks of gestation, the human heart muscle is supposed to compress into a thick, compact mass, but that shift doesnt happen correctly in LVNC patients. Earlier studies gave conflicting information about why: maybe the heart muscle cells were proliferating too little, or maybe too much.

Another mystery about the disease is its range of severity, which varies from no symptoms at all to complete heart failure. As the new paper describes, the family who agreed to have their cells studied is a good example. Of three siblings who donated cells for research, one had already had a heart transplant, while the other two had hearts that pumped normally in spite of deeper trabeculations (the scientific word for the spongy formations). Meanwhile, their father had an enlarged heart, but no sponginess in his heart muscle and no other symptoms.

Using the heart muscle cells derived from all four people, the researchers identified the gene defect that causes LVNC in this family; it codes for a cardiac transcription factor or a protein that controls the expression of other genes called TBX20. The scientists conducted several experiments to figure out how the TBX20 abnormality changes heart muscle cell proliferation with the abnormality, the cells dont proliferate enough, it turns out. They also explored the exact signaling pathways that cause the problem, showing that the magnitude of signaling abnormalities could explain differences in symptom severity between family members. They created a mouse model with the familys gene defect for further characterization, and also showed that blocking the faulty signal from the altered TBX20 could restore the mutated cells ability to proliferate. Its possible that some day, they might be able to turn these findings into a drug that could correct heart muscle formation in affected fetuses before birth.

The new findings still leave unanswered questions about the origins of LVNC. Cardiologists suspect the problem can arise in several ways, and theyll need to study many more families to find out if TBX20 mutations are a common or rare cause. But the paper does demonstrate how induced pluripotent stem cells can overcome a research hurdle, and suggests that the same methods could help scientists tackling other hard-to-study conditions.

This study shows the feasibility of modeling such developmental defects using human tissue-specific cells, rather than relying on animal cells or animal models, Wu said. It opens up an exciting new avenue for research into congenital heart disease that could help literally the youngest in utero patients.

Previously: One of the most promising minds of his generation: Joseph Wu takes stem cells to heart, Stem cells create faithful replicas of native tissue, according to Stanford study and A cheaper, faster way to find genetic defects in heart patients Photo by amanda tipton

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How Does A Heart Defect Start? Stanford Scientists Use ...

Cardiac Stem Cells Comments Off on How Does A Heart Defect Start? Stanford Scientists Use … | September 21st, 2016

14th International Conference on Clinical & Experimental Cardiology is among the Worlds leading Scientific Conference. The three day event on Cardiology practices will host 60+ Scientific and technical sessions and sub-sessions on cutting edge research and latest research innovations in the field of cardiology and cardiac surgeries across the globe. This year annual Cardiology conference will comprises of 14 major sessions designed to offer comprehensive sessions that address current issues in various field of Cardiology. The attendees can find some- Exclusive Sessions and Panel discussions on latest innovations in Cardiac Surgeries and Heart Failure. This is the excellent platform to showcase the latest products and formulations in the field of Cardiology.

Theme:The Science of Heart Discovery

Scientific sessions:

Track: Clinical Cardiology

Cardiology is a branch of medicine dealing with disorders of the heart be it human or animal. The field includes medical diagnosis and treatment of congenital heart defects, coronary artery disease, heart failure, valvular heart disease and electrophysiology. Physicians who specialize in this field of medicine are called cardiologists, a specialty of internal medicine. Pediatric cardiologists are pediatricians who specialize in cardiology. Physicians who specialize in cardiac surgery are called cardiothoracic surgeons or cardiac surgeons, a specialty of general surgery. Clinical Cardiology is an American journal about Cardiology founded in 1978. It provides a forum for the coordination of clinical research in diagnostics, cardiovascular medicine and cardiovascular surgery.

RelevantConferences:9thArrhythmiasConference July 14-15, 2016 Brisbane, Australia;CardioVascular MedicineConference August 01-02, 2016 Manchester, UK;EchocardiographyConference July 18-19, 2016 Berlin, Germany; 8th Global Cardiologists Annual Meeting July 18-20, 2016 Berlin, Germany; Atherosclerosis and Clinical Cardiology Conference July 11-12, 2016 Philadelphia, Pennsylvania, USA; Ischemic Heart Diseases Conference October 20-21, 2016 Chicago, Illinois, USA; Hypertension & Health Care Conference August 11-12, 2016 Toronto, Canada; 11thCardiac Conference September 12-13, 2016 Philadelphia, Pennsylvania, USA; 13thEuropean Cardiology Congress October 17-19, 2016 Rome, Italy; 19th Annual Update on Pediatric and Congenital Cardiovascular Disease February 24- 28, 2016, Orlando, USA; American Cardiology Congress 2016; ACC Annual Meeting 2016; American Cardiology Congress 2016; European Cardiology Congress August 27 - 31, 2016 Rome, Italy; International Conference and Expo on Cardiology and Cardiac surgery April 04-06, 2016, Dubai, UAE; 21st World Congress on Heart Disease, July 30-August 1, 2016, Boston, MA, USA.

Track:Heart Failure

Heart failure is a condition caused by the heart failing to pump enough blood around the body at the right pressure. It usually occurs because the heart muscle has become too weak or stiff to work properly. If you have heart failure, it does not mean your heart is about to stop working. It means the heart needs some support to do its job, usually in the form of medicines. Breathlessness, feeling very tired and ankle swelling is the main symptoms of heart failure. But all of these symptoms can have other causes, only some of which are serious. The symptoms of heart failure can develop quickly (acute heart failure). If this happens, you will need to be treated in hospital. But they can also develop gradually (chronic heart failure). The most common causes are heart attack, high blood pressure, cardiomyopathy (diseases of the heart muscle. Sometimes these are inherited from your family and sometimes they are caused by other things, such as viral infections).

RelevantConferences:9thArrhythmiasConference July 14-15, 2016 Brisbane, Australia;CardioVascular MedicineConference August 01-02, 2016 Manchester, UK;EchocardiographyConference July 18-19, 2016 Berlin, Germany; 8th Global Cardiologists Annual Meeting July 18-20, 2016 Berlin, Germany; Atherosclerosis and Clinical Cardiology Conference July 11-12, 2016 Philadelphia, Pennsylvania, USA; Ischemic Heart Diseases Conference October 20-21, 2016 Chicago, Illinois, USA; Hypertension & Health Care Conference August 11-12, 2016 Toronto, Canada; 11thCardiac Conference September 12-13, 2016 Philadelphia, Pennsylvania, USA; 13thEuropean Cardiology Congress October 17-19, 2016 Rome, Italy; 19th Annual Update on Pediatric and Congenital Cardiovascular Disease February 24- 28, 2016, Orlando, USA; American Cardiology Congress 2016; ACC Annual Meeting 2016; American Cardiology Congress 2016; European Cardiology Congress August 27 - 31, 2016 Rome, Italy; International Conference and Expo on Cardiology and Cardiac surgery April 04-06, 2016, Dubai, UAE; 21st World Congress on Heart Disease, July 30-August 1, 2016, Boston, MA, USA.

Track:Heart Diseases

Heart disease include heart diseases that is any type of disorder that affects the heart. Heart disease meetings comes under cardiology conferences that comprises the heart diseases tracks that means the same as cardiac disease but not the cardiovascular diseases. This condition results from a buildup of plaque on the inside of the arteries, which reduces blood flow to the heart and increases the risk of a heart attack and other heart complications. In this sub topic Heart disease we have different types of heart diseases i.e. Coronary heart diseases, Pediatric heart diseases, Congenital Heart Diseases, myocardial infarction etc.

RelevantConferences:9thArrhythmiasConference July 14-15, 2016 Brisbane, Australia;CardioVascular MedicineConference August 01-02, 2016 Manchester, UK;EchocardiographyConference July 18-19, 2016 Berlin, Germany; 8th Global Cardiologists Annual Meeting July 18-20, 2016 Berlin, Germany; Atherosclerosis and Clinical Cardiology Conference July 11-12, 2016 Philadelphia, Pennsylvania, USA; Ischemic Heart Diseases Conference October 20-21, 2016 Chicago, Illinois, USA; Hypertension & Health Care Conference August 11-12, 2016 Toronto, Canada; 11thCardiac Conference September 12-13, 2016 Philadelphia, Pennsylvania, USA; 13thEuropean Cardiology Congress October 17-19, 2016 Rome, Italy; 19th Annual Update on Pediatric and Congenital Cardiovascular Disease February 24- 28, 2016, Orlando, USA; American Cardiology Congress 2016; ACC Annual Meeting 2016; American Cardiology Congress 2016; European Cardiology Congress August 27 - 31, 2016 Rome, Italy; International Conference and Expo on Cardiology and Cardiac surgery April 04-06, 2016, Dubai, UAE; 21st World Congress on Heart Disease, July 30-August 1, 2016, Boston, MA, USA.

Track:Obesity and Heart

People with a body mass index (BMI) of 30 or higher are considered obese. The term obesity is used to describe the health condition of anyone significantly above his or her ideal healthy weight. Obesity increases the risk for heart disease and stroke. But it harms more than just the heart and blood vessel system. It's also a major cause of gallstones, osteoarthritis and respiratory problems. Obesity is intimately intertwined with multiple health conditions that underlie cardiovascular disease including high blood pressure, diabetes, and abnormal blood cholesterol. In addition, weight gain is a frequent consequence of heart-damaging lifestyle choices such as lack of exercise and a fat-laden diet. Obesity also can lead to heart failure. This is a serious condition in which your heart can't pump enough blood to meet your body's needs.

RelevantConferences:9thArrhythmiasConference July 14-15, 2016 Brisbane, Australia;CardioVascular MedicineConference August 01-02, 2016 Manchester, UK;EchocardiographyConference July 18-19, 2016 Berlin, Germany; 8th Global Cardiologists Annual Meeting July 18-20, 2016 Berlin, Germany; Atherosclerosis and Clinical Cardiology Conference July 11-12, 2016 Philadelphia, Pennsylvania, USA; Ischemic Heart Diseases Conference October 20-21, 2016 Chicago, Illinois, USA; Hypertension & Health Care Conference August 11-12, 2016 Toronto, Canada; 11thCardiac Conference September 12-13, 2016 Philadelphia, Pennsylvania, USA; 13thEuropean Cardiology Congress October 17-19, 2016 Rome, Italy; 19th Annual Update on Pediatric and Congenital Cardiovascular Disease February 24- 28, 2016, Orlando, USA; American Cardiology Congress 2016; ACC Annual Meeting 2016; American Cardiology Congress 2016; European Cardiology Congress August 27 - 31, 2016 Rome, Italy; International Conference and Expo on Cardiology and Cardiac surgery April 04-06, 2016, Dubai, UAE; 21st World Congress on Heart Disease, July 30-August 1, 2016, Boston, MA, USA.

Track:Cardiac Drugs

Cardiac Drugs are the drugs which are used in any way to treat conditions of the heart or the circulatory or vascular system. Many classes of cardiovascular agents are available to treat the various cardiovascular conditions. They are a complicated group of drugs with many being used for multiple heart conditions. Prescription drugs and medicines for diseases relating to the structure and function of the heart and blood vessels. In this sub topic we have Sodium, potassium, calcium channel blockers, ACE-inhibitors and Cardiac biomarkers. There are 6 associations and societies and the main association for Cardiac Therapeutic Agents in USA. 50 universities are working on Cardiac Therapeutic Agents. There are 120 Companies in USA that are making Cardiac Therapeutic Agents in Cardiology. 3new drugs were introduced in 2015. There are many types of cardiovascular drugs in the market that include Cardiac glycosides, antiarrhythmic agents, antianginal agents and antihypertensive agents.

RelevantConferences:9thArrhythmiasConference July 14-15, 2016 Brisbane, Australia;CardioVascular MedicineConference August 01-02, 2016 Manchester, UK;EchocardiographyConference July 18-19, 2016 Berlin, Germany; 8th Global Cardiologists Annual Meeting July 18-20, 2016 Berlin, Germany; Atherosclerosis and Clinical Cardiology Conference July 11-12, 2016 Philadelphia, Pennsylvania, USA; Ischemic Heart Diseases Conference October 20-21, 2016 Chicago, Illinois, USA; Hypertension & Health Care Conference August 11-12, 2016 Toronto, Canada; 11thCardiac Conference September 12-13, 2016 Philadelphia, Pennsylvania, USA; 13thEuropean Cardiology Congress October 17-19, 2016 Rome, Italy; 19th Annual Update on Pediatric and Congenital Cardiovascular Disease February 24- 28, 2016, Orlando, USA; American Cardiology Congress 2016; ACC Annual Meeting 2016; American Cardiology Congress 2016; European Cardiology Congress August 27 - 31, 2016 Rome, Italy; International Conference and Expo on Cardiology and Cardiac surgery April 04-06, 2016, Dubai, UAE; 21st World Congress on Heart Disease, July 30-August 1, 2016, Boston, MA, USA.

Track:Cardiac Imaging and technology

Advances in imaging technology have sparked fundamental changes in the approach to cardiac care. One of the most accurate diagnostic techniques cardiac imaging employs new, non-invasive and minimally invasive radiology technology to produce three-dimensional images of the heart. The imaging tools help to discover medical problems that several years ago were undetectable using conventional methods of diagnosis. Cardiac imaging techniques include coronary catheterization, echocardiogram, and intravascular ultrasound.

RelevantConferences:9thArrhythmiasConference July 14-15, 2016 Brisbane, Australia;CardioVascular MedicineConference August 01-02, 2016 Manchester, UK;EchocardiographyConference July 18-19, 2016 Berlin, Germany; 8th Global Cardiologists Annual Meeting July 18-20, 2016 Berlin, Germany; Atherosclerosis and Clinical Cardiology Conference July 11-12, 2016 Philadelphia, Pennsylvania, USA; Ischemic Heart Diseases Conference October 20-21, 2016 Chicago, Illinois, USA; Hypertension & Health Care Conference August 11-12, 2016 Toronto, Canada; 11thCardiac Conference September 12-13, 2016 Philadelphia, Pennsylvania, USA; 13thEuropean Cardiology Congress October 17-19, 2016 Rome, Italy; 19th Annual Update on Pediatric and Congenital Cardiovascular Disease February 24- 28, 2016, Orlando, USA; American Cardiology Congress 2016; ACC Annual Meeting 2016; American Cardiology Congress 2016; European Cardiology Congress August 27 - 31, 2016 Rome, Italy; International Conference and Expo on Cardiology and Cardiac surgery April 04-06, 2016, Dubai, UAE; 21st World Congress on Heart Disease, July 30-August 1, 2016, Boston, MA, USA.

Track:Women & CVD

Cardiovascular disease (CVD) heart disease and stroke is the biggest killer of women globally, killing more women than all cancers, tuberculosis, HIV/AIDS and malaria combined. Heart disease is the leading cause of death for women in the United States, killing 292,188 women in 2009 thats 1 in every 4 female deaths. While some women have no symptoms, others experience angina (dull, heavy to sharp chest pain or discomfort), pain in the neck/jaw/throat or pain in the upper abdomen or back. These may occur during rest, begin during physical activity, or be triggered by mental stress. Sometimes heart disease may be silent and not diagnosed until a woman experiences signs or symptoms of a heart attack, heart failure, an arrhythmia or stroke. Women with diabetes have higher CVD mortality rates than men with diabetes. Women who engage in physical activity for less than an hour per week have 1.48 times the risk of developing coronary heart disease, compared to women who do more than three hours of physical activity per week. Go Red for Women is a major international awareness campaign dedicated to the prevention, diagnosis and control of heart disease and stroke in women.

RelevantConferences:9thArrhythmiasConference July 14-15, 2016 Brisbane, Australia;CardioVascular MedicineConference August 01-02, 2016 Manchester, UK;EchocardiographyConference July 18-19, 2016 Berlin, Germany; 8th Global Cardiologists Annual Meeting July 18-20, 2016 Berlin, Germany; Atherosclerosis and Clinical Cardiology Conference July 11-12, 2016 Philadelphia, Pennsylvania, USA; Ischemic Heart Diseases Conference October 20-21, 2016 Chicago, Illinois, USA; Hypertension & Health Care Conference August 11-12, 2016 Toronto, Canada; 11thCardiac Conference September 12-13, 2016 Philadelphia, Pennsylvania, USA; 13thEuropean Cardiology Congress October 17-19, 2016 Rome, Italy; 19th Annual Update on Pediatric and Congenital Cardiovascular Disease February 24- 28, 2016, Orlando, USA; American Cardiology Congress 2016; ACC Annual Meeting 2016; American Cardiology Congress 2016; European Cardiology Congress August 27 - 31, 2016 Rome, Italy; International Conference and Expo on Cardiology and Cardiac surgery April 04-06, 2016, Dubai, UAE; 21st World Congress on Heart Disease, July 30-August 1, 2016, Boston, MA, USA.

Track:Pediatric Cardiology

Pediatric Cardiology is responsible for the diagnosis of congenital heart defects, performing diagnostic procedures such as echocardiograms, cardiac catheterizations, and for the ongoing management of the sequel of heart disease in infants, children and adolescents. The division is actively involved in research aimed at preventing both congenital and acquired heart disease in children. Finally, the division is committed to educating the next generation of physicians, and offers advanced training in pediatric cardiology.

RelevantConferences:9thArrhythmiasConference July 14-15, 2016 Brisbane, Australia;CardioVascular MedicineConference August 01-02, 2016 Manchester, UK;EchocardiographyConference July 18-19, 2016 Berlin, Germany; 8th Global Cardiologists Annual Meeting July 18-20, 2016 Berlin, Germany; Atherosclerosis and Clinical Cardiology Conference July 11-12, 2016 Philadelphia, Pennsylvania, USA; Ischemic Heart Diseases Conference October 20-21, 2016 Chicago, Illinois, USA; Hypertension & Health Care Conference August 11-12, 2016 Toronto, Canada; 11thCardiac Conference September 12-13, 2016 Philadelphia, Pennsylvania, USA; 13thEuropean Cardiology Congress October 17-19, 2016 Rome, Italy; 19th Annual Update on Pediatric and Congenital Cardiovascular Disease February 24- 28, 2016, Orlando, USA; American Cardiology Congress 2016; ACC Annual Meeting 2016; American Cardiology Congress 2016; European Cardiology Congress August 27 - 31, 2016 Rome, Italy; International Conference and Expo on Cardiology and Cardiac surgery April 04-06, 2016, Dubai, UAE; 21st World Congress on Heart Disease, July 30-August 1, 2016, Boston, MA, USA.

Track:Cardiac Nursing

Cardiac nursing is a nursing specialty that works with patients who suffer from various conditions of the cardiovascular system. Cardiac nurses help treat conditions such as unstable angina, cardiomyopathy, coronary artery disease, congestive heart failure, myocardial infarction and cardiac dysrhythmia under the direction of a cardiologist. Cardiac nurses perform postoperative care on a surgical unit, stress test evaluations, cardiac monitoring, vascular monitoring, and health assessments. Cardiac nurses work in many different environments, including coronary care units (CCU), cardiac catheterization, intensive care units (ICU), operating theatres, cardiac rehabilitation centers, clinical research, cardiac surgery wards, cardiovascular intensive care units (CVICU), and cardiac medical wards.

RelevantConferences:9thArrhythmiasConference July 14-15, 2016 Brisbane, Australia;CardioVascular MedicineConference August 01-02, 2016 Manchester, UK;EchocardiographyConference July 18-19, 2016 Berlin, Germany; 8th Global Cardiologists Annual Meeting July 18-20, 2016 Berlin, Germany; Atherosclerosis and Clinical Cardiology Conference July 11-12, 2016 Philadelphia, Pennsylvania, USA; Ischemic Heart Diseases Conference October 20-21, 2016 Chicago, Illinois, USA; Hypertension & Health Care Conference August 11-12, 2016 Toronto, Canada; 11thCardiac Conference September 12-13, 2016 Philadelphia, Pennsylvania, USA; 13thEuropean Cardiology Congress October 17-19, 2016 Rome, Italy; 19th Annual Update on Pediatric and Congenital Cardiovascular Disease February 24- 28, 2016, Orlando, USA; American Cardiology Congress 2016; ACC Annual Meeting 2016; American Cardiology Congress 2016; European Cardiology Congress August 27 - 31, 2016 Rome, Italy; International Conference and Expo on Cardiology and Cardiac surgery April 04-06, 2016, Dubai, UAE; 21st World Congress on Heart Disease, July 30-August 1, 2016, Boston, MA, USA.

Track:Diabetic Cardiovascular Diseases

The term diabetic heart disease (DHD) refers to heart disease that develops in people who have diabetes. Diabetes is a disease in which the body's blood glucose (sugar) level is too high. Normally, the body breaks down food into glucose and carries it to cells throughout the body. The cells use a hormone called insulin to turn the glucose into energy. There is a clear-cut relationship between diabetes and cardiovascular disease. Coronary heart disease is recognized to be the cause of death for 80% of people with diabetes; however, the NHS states that heart attacks are largely preventable. Cardiovascular disease is the leading cause of mortality for people with diabetes. Hypertension, abnormal blood lipids and obesity, all risk factors in their own right for cardiovascular disease, occur more frequently in people with diabetes. Several advances in treating heart disease over the past two decades have improved the chances of surviving a heart attack or stroke. However, as the incidence of diabetes steadily increases, so does the number of new cases of heart disease and cardiovascular complications.

RelevantConferences:9thArrhythmiasConference July 14-15, 2016 Brisbane, Australia;CardioVascular MedicineConference August 01-02, 2016 Manchester, UK;EchocardiographyConference July 18-19, 2016 Berlin, Germany; 8th Global Cardiologists Annual Meeting July 18-20, 2016 Berlin, Germany; Atherosclerosis and Clinical Cardiology Conference July 11-12, 2016 Philadelphia, Pennsylvania, USA; Ischemic Heart Diseases Conference October 20-21, 2016 Chicago, Illinois, USA; Hypertension & Health Care Conference August 11-12, 2016 Toronto, Canada; 11thCardiac Conference September 12-13, 2016 Philadelphia, Pennsylvania, USA; 13thEuropean Cardiology Congress October 17-19, 2016 Rome, Italy; 19th Annual Update on Pediatric and Congenital Cardiovascular Disease February 24- 28, 2016, Orlando, USA; American Cardiology Congress 2016; ACC Annual Meeting 2016; American Cardiology Congress 2016; European Cardiology Congress August 27 - 31, 2016 Rome, Italy; International Conference and Expo on Cardiology and Cardiac surgery April 04-06, 2016, Dubai, UAE; 21st World Congress on Heart Disease, July 30-August 1, 2016, Boston, MA, USA.

Track:Cardiac Surgery

Cardiovascular surgery is surgery on the heart or great vessels performed by cardiac surgeons. Frequently, it is done to treat complications of ischemic heart disease (for example, coronary artery bypass grafting), correct congenital heart disease, or treat valvular heart disease from various causes including endocarditis, rheumatic heart disease and atherosclerosis. It also includes heart transplantation. The development of cardiac surgery and cardiopulmonary bypass techniques has reduced the mortality rates of these surgeries to relatively low ranks. Coronary artery bypass grafting (CABG) is the most common type of heart surgery. CABG improves blood flow to the heart. Surgeons use CABG to treat people who have severe coronary heart disease (CHD).

RelevantConferences:9thArrhythmiasConference July 14-15, 2016 Brisbane, Australia;CardioVascular MedicineConference August 01-02, 2016 Manchester, UK;EchocardiographyConference July 18-19, 2016 Berlin, Germany; 8th Global Cardiologists Annual Meeting July 18-20, 2016 Berlin, Germany; Atherosclerosis and Clinical Cardiology Conference July 11-12, 2016 Philadelphia, Pennsylvania, USA; Ischemic Heart Diseases Conference October 20-21, 2016 Chicago, Illinois, USA; Hypertension & Health Care Conference August 11-12, 2016 Toronto, Canada; 11thCardiac Conference September 12-13, 2016 Philadelphia, Pennsylvania, USA; 13thEuropean Cardiology Congress October 17-19, 2016 Rome, Italy; 19th Annual Update on Pediatric and Congenital Cardiovascular Disease February 24- 28, 2016, Orlando, USA; American Cardiology Congress 2016; ACC Annual Meeting 2016; American Cardiology Congress 2016; European Cardiology Congress August 27 - 31, 2016 Rome, Italy; International Conference and Expo on Cardiology and Cardiac surgery April 04-06, 2016, Dubai, UAE; 21st World Congress on Heart Disease, July 30-August 1, 2016, Boston, MA, USA.

Track:Current Research in Cardiology

Advances in medicine means that if CHD is detected at an early stage it can be treated successfully to extend the survival rate. Successful treatment is more likely if the disease is detected at its earliest stages. Our current research focuses on the early detection of CHD in order to halt or reverse the progress of the disease. The ongoing research includes pioneering the use of heart scanning in the early diagnosis of heart disease in diabetics, Development of Nuclear Cardiology techniques for the detection of heart disease, Drug development and evaluation of treatments used in heart disease, Identification of novel biological markers to predict the presence of heart disease, analysis of ethnic and socio-economic differences in heart disease risk.

RelevantConferences:9thArrhythmiasConference July 14-15, 2016 Brisbane, Australia;CardioVascular MedicineConference August 01-02, 2016 Manchester, UK;EchocardiographyConference July 18-19, 2016 Berlin, Germany; 8th Global Cardiologists Annual Meeting July 18-20, 2016 Berlin, Germany; Atherosclerosis and Clinical Cardiology Conference July 11-12, 2016 Philadelphia, Pennsylvania, USA; Ischemic Heart Diseases Conference October 20-21, 2016 Chicago, Illinois, USA; Hypertension & Health Care Conference August 11-12, 2016 Toronto, Canada; 11thCardiac Conference September 12-13, 2016 Philadelphia, Pennsylvania, USA; 13thEuropean Cardiology Congress October 17-19, 2016 Rome, Italy; 19th Annual Update on Pediatric and Congenital Cardiovascular Disease February 24- 28, 2016, Orlando, USA; American Cardiology Congress 2016; ACC Annual Meeting 2016; American Cardiology Congress 2016; European Cardiology Congress August 27 - 31, 2016 Rome, Italy; International Conference and Expo on Cardiology and Cardiac surgery April 04-06, 2016, Dubai, UAE; 21st World Congress on Heart Disease, July 30-August 1, 2016, Boston, MA, USA.

Track:Cardiologists Training & Education

Cardiologists provide health care to prevent, diagnose and treat diseases and conditions of the heart and cardiovascular system, including the arteries. Because the field of cardiology encompasses so many different types of diseases and procedures, there are many different types of cardiology one may choose to practice depending on his or her interests and skill sets, and the type of work theyd like to do. Cardiologists receive extensive education, including four years of medical school and three years of training in general internal medicine. After this, a cardiologist spends three or more years in specialized training. Many cardiologists are specially trained in this technique, but others specialize in office diagnosis, the performance and interpretation of echocardiograms, ECGs, and exercise tests. Still others have special skill in cholesterol management or cardiac rehabilitation and fitness. All cardiologists know how and when these tests are needed and how to manage cardiac emergencies.

RelevantConferences:9thArrhythmiasConference July 14-15, 2016 Brisbane, Australia;CardioVascular MedicineConference August 01-02, 2016 Manchester, UK;EchocardiographyConference July 18-19, 2016 Berlin, Germany; 8th Global Cardiologists Annual Meeting July 18-20, 2016 Berlin, Germany; Atherosclerosis and Clinical Cardiology Conference July 11-12, 2016 Philadelphia, Pennsylvania, USA; Ischemic Heart Diseases Conference October 20-21, 2016 Chicago, Illinois, USA; Hypertension & Health Care Conference August 11-12, 2016 Toronto, Canada; 11thCardiac Conference September 12-13, 2016 Philadelphia, Pennsylvania, USA; 13thEuropean Cardiology Congress October 17-19, 2016 Rome, Italy; 19th Annual Update on Pediatric and Congenital Cardiovascular Disease February 24- 28, 2016, Orlando, USA; American Cardiology Congress 2016; ACC Annual Meeting 2016; American Cardiology Congress 2016; European Cardiology Congress August 27 - 31, 2016 Rome, Italy; International Conference and Expo on Cardiology and Cardiac surgery April 04-06, 2016, Dubai, UAE; 21st World Congress on Heart Disease, July 30-August 1, 2016, Boston, MA, USA.

Track:Advances in Cardiologists Education

Advances in Cardiology Education presents the current thinking of international experts regarding the underlying mechanisms of cardiovascular risk and the pathogenesis and pathophysiology of heart and its related disorders. This session gives new insights into the relationship between arterial stiffness, cardiovascular diagnosis, vascular study and atherosclerosis, but also establishes the possible interactions with age and other cardiovascular factors such as high blood pressure, diabetes and hyperlipidemia.

RelevantConferences:9thArrhythmiasConference July 14-15, 2016 Brisbane, Australia;CardioVascular MedicineConference August 01-02, 2016 Manchester, UK;EchocardiographyConference July 18-19, 2016 Berlin, Germany; 8th Global Cardiologists Annual Meeting July 18-20, 2016 Berlin, Germany; Atherosclerosis and Clinical Cardiology Conference July 11-12, 2016 Philadelphia, Pennsylvania, USA; Ischemic Heart Diseases Conference October 20-21, 2016 Chicago, Illinois, USA; Hypertension & Health Care Conference August 11-12, 2016 Toronto, Canada; 11thCardiac Conference September 12-13, 2016 Philadelphia, Pennsylvania, USA; 13thEuropean Cardiology Congress October 17-19, 2016 Rome, Italy; 19th Annual Update on Pediatric and Congenital Cardiovascular Disease February 24- 28, 2016, Orlando, USA; American Cardiology Congress 2016; ACC Annual Meeting 2016; American Cardiology Congress 2016; European Cardiology Congress August 27 - 31, 2016 Rome, Italy; International Conference and Expo on Cardiology and Cardiac surgery April 04-06, 2016, Dubai, UAE; 21st World Congress on Heart Disease, July 30-August 1, 2016, Boston, MA, USA.

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Cardiology Conferences | Events | Meetings | Florida | USA ...

Cardiac Stem Cells Comments Off on Cardiology Conferences | Events | Meetings | Florida | USA … | September 8th, 2016

Effat MA: Pathophysiology of ischemic heart disease: an overview.

AACN Clin Issues 1995, 6:369-74. PubMedAbstract | PublisherFullText

Chi NC, Karliner JS: Molecular determinants of responses to myocardial ischemia/reperfusion injury: focus on hypoxia-inducible and heat shock factors.

Cardiovasc Res 2004, 61:437-47. PubMedAbstract | PublisherFullText

Frangogiannis NG: The immune system and cardiac repair.

Pharmacol Res 2008, 58:88-111. PubMedAbstract | PublisherFullText

Ghadge SK, Muhlstedt S, Ozcelik C, Bader M: SDF-1alpha as a therapeutic stem cell homing factor in myocardial infarction.

Pharmacol Therapeut 2011, 129:97-108.

Hartwell D, Colquitt J, Loveman E, Clegg AJ, Brodin H, Waugh N, et al.: Clinical effectiveness and cost-effectiveness of immediate angioplasty for acute myocardial infarction: systematic review and economic evaluation.

Health Technol Assess 2005, 9:1-99.

Evans RW: Socioeconomic aspects of heart transplantation.

Curr Opin Cardiol 1995, 10:169-79. PubMedAbstract | PublisherFullText

Segers VF, Lee RT: Stem-cell therapy for cardiac disease.

Nature 2008, 451:937-42. PubMedAbstract | PublisherFullText

Gnecchi M, Zhang Z, Ni A, Dzau VJ: Paracrine mechanisms in adult stem cell signaling and therapy.

Circ Res 2008, 103:1204-19. PubMedAbstract | PublisherFullText

Manuilova ES, Gordeeva OF, Grivennikov IA, Ozernyuk ND: Embryonic stem cells: spontaneous and directed differentiation.

Biol Bull Russ Acad Sci 2001, 28:595-600.

Li R, Xue T, Cho H, Akar F, Tsang S, Jones S, et al.: Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: insights into the development of cell-based pacemakers.

Circulation 2005, 111:11-20. PubMedAbstract | PublisherFullText

Chen A, Ting S, Seow J, Reuveny S, Oh S. Considerations in designing systems for large scale production of human cardiomyocytes from pluripotent stem cells. Stem Cell Res Ther. 2014;5:122.

Bernstein HS. Cardiac repair and restoration using human embryonic stem cells. Regen Med. 2012;7:697.

He W, Ye L, Li S, Liu H, Wang Q, Fu X, et al.: Stirred suspension culture improves embryoid body formation and cardiogenic differentiation of genetically modified embryonic stem cells.

Biol Pharmaceut Bull 2012, 35:308-16.

Chong JJ, Yang X, Don CW, Minami E, Liu YW, Weyers JJ, et al.: Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts.

Nature 2014, 510:273-7. PubMedAbstract | PublisherFullText

Robertson JA: Human embryonic stem cell research: ethical and legal issues.

Nat Rev Genet 2001, 2:74-8. PubMedAbstract | PublisherFullText

Dhar D, Hsi-en HJ: Stem cell research policies around the world.

Yale J Biol Med 2009, 82:113-5. PubMedAbstract | PublisherFullText

Marelli D, Desrosiers C, el-Alfy M, Kao RL, Chiu RC: Cell transplantation for myocardial repair: an experimental approach.

Cell Transplant 1992, 1:383-90. PubMedAbstract | PublisherFullText

Reinecke H, Poppa V, Murry CE: Skeletal muscle stem cells do not transdifferentiate into cardiomyocytes after cardiac grafting.

J Mol Cell Cardiol 2002, 34:241-9. PubMedAbstract | PublisherFullText

Pagani FD, DerSimonian H, Zawadzka A, Wetzel K, Edge AS, Jacoby DB, et al.: Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation.

J Am Coll Cardiol 2003, 41:879-88. PubMedAbstract | PublisherFullText

Menasche P, Alfieri O, Janssens S, McKenna W, Reichenspurner H, Trinquart L, et al.: The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation.

Circulation 2008, 117:1189-200. PubMedAbstract | PublisherFullText

Roell W, Lewalter T, Sasse P, Tallini YN, Choi BR, Breitbach M, et al.: Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia.

Nature 2007, 450:819-24. PubMedAbstract | PublisherFullText

Fernandes S, Rijen HVMV, Forest V, Evain S, Leblond A, Mrot J, et al.: Cardiac cell therapy: overexpression of connexin43 in skeletal myoblasts and prevention of ventricular arrhythmias.

J Cell Mol Med 2009, 13:3703-12. PubMedAbstract | PublisherFullText

Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson S, Li B, et al.: Bone marrow cells regenerate infarcted myocardium.

Nature 2001, 410:701-5. PubMedAbstract | PublisherFullText

Murry C, Soonpaa M, Reinecke H, Nakajima H, Rubart M, Pasumarthi K, et al.: Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts.

Nature 2004, 428:664-8. PubMedAbstract | PublisherFullText

Fukuda K, Fujita J: Mesenchymal, but not hematopoietic, stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction in mice.

Kidney Int 2005, 68:1940-3. PubMedAbstract | PublisherFullText

Nygren JM, Jovinge S, Breitbach M, Sawen P, Roll W, Hescheler J, et al.: Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation.

Nat Med 2004, 10:494-501. PubMedAbstract | PublisherFullText

Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC: Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium.

Nature 2004, 428:668-73. PubMedAbstract | PublisherFullText

Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, et al.: AC133, a novel marker for human hematopoietic stem and progenitor cells.

Blood 1997, 90:5002-12. PubMedAbstract | PublisherFullText

Sidney LE, Branch MJ, Dunphy SE, Dua HS, Hopkinson A: Concise review: Evidence for CD34 as a common marker for diverse progenitors.

Stem Cells 2014, 32:1380-9. PubMedAbstract | PublisherFullText

Krbling M, Katz RL, Khanna A, Ruifrok AC, Rondon G, Albitar M, et al.: Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells.

N Engl J Med 2002, 346:738-46. PubMedAbstract | PublisherFullText

Yeh ET, Zhang S, Wu HD, Korbling M, Willerson JT, Estrov Z: Transdifferentiation of human peripheral blood CD34+enriched cell population into cardiomyocytes, endothelial cells, and smooth muscle cells in vivo.

Circulation 2003, 108:2070-3. PubMedAbstract | PublisherFullText

Norol F, Bonnet N, Peinnequin A, Chretien F, Legrand R, Isnard R, et al.: GFP-transduced CD34+ and Lin- CD34- hematopoietic stem cells did not adopt a cardiac phenotype in a nonhuman primate model of myocardial infarct.

Exp Hematol 2007, 35:653-61. PubMedAbstract | PublisherFullText

Arnous S, Mozid A, Martin J, Mathur A: Bone marrow mononuclear cells and acute myocardial infarction.

Stem Cell Res Ther 2012, 3:2. PubMedAbstract | PublisherFullText

Clifford DM, Fisher SA, Brunskill SJ, Doree C, Mathur A, Watt S, et al. Stem cell treatment for acute myocardial infarction. Cochrane Database Syst Rev. 2012;2:Cd006536.

Fisher SA, Brunskill SJ, Doree C, Mathur A, Taggart DP, Martin-Rendon E: Stem cell therapy for chronic ischaemic heart disease and congestive heart failure.

Cochrane Database Syst Rev 2014, 4:CD007888. PubMedAbstract | PublisherFullText

Uemura R, Xu M, Ahmad N, Ashraf M: Bone marrow stem cells prevent left ventricular remodelling of ischemic heart through paracrine signalling.

Circ Res 2006, 98:1414-21. PubMedAbstract | PublisherFullText

Nowbar AN, Mielewczik M, Karavassilis M, Dehbi H-M, Shun-Shin MJ, Jones S, et al.: Discrepancies in autologous bone marrow stem cell trials and enhancement of ejection fraction (DAMASCENE): weighted regression and meta-analysis.

BMJ 2014, 348:g2688. PubMedAbstract | PublisherFullText

Abbott A: Doubts over heart stem-cell therapy.

Nature 2014, 509:15-6. PubMedAbstract | PublisherFullText

Pittenger MF: Multilineage potential of adult human mesenchymal stem cells.

Science 1999, 284:143-7. PubMedAbstract | PublisherFullText

Long X, Olszewski M, Huang W, Kletzel M: Neural cell differentiation in vitro from adult human bone marrow mesenchymal stem cells.

Stem Cells Dev 2005, 14:65-9. PubMedAbstract | PublisherFullText

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al.: Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

Cytotherapy 2006, 8:315-7. PubMedAbstract | PublisherFullText

Kuraitis D, Ruel M, Suuronen EJ: Mesenchymal stem cells for cardiovascular regeneration.

Cardiovasc Drugs Ther 2011, 25:349-62. PubMedAbstract | PublisherFullText

Miyahara Y, Nagaya N, Kataoka M, Yanagawa B, Tanaka K, Hao H, et al.: Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction.

Nat Med 2006, 12:459-65. PubMedAbstract | PublisherFullText

Takahashi K, Yamanaka S: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

Cell 2006, 126:663-76. PubMedAbstract | PublisherFullText

Lee J-H, Lee JB, Shapovalova Z, Fiebig-Comyn A, Mitchell RR, Laronde S, et al.: Somatic transcriptome priming gates lineage-specific differentiation potential of human-induced pluripotent stem cell states.

Nat Commun 2014, 5:5605. PubMedAbstract | PublisherFullText

Martens A, Kensah G, Rojas S, Rotrmel A, Baraki H, Haverich A, et al.: Induced pluripotent stem cell (iPSC)-derived cardiomyocytes engraft and improve heart function in a mouse model of acute myocardial infarction.

Thorac Cardiovasc Surg 2012, 60:PP26.

Yu SP, Wei Z, Wei L: Preconditioning strategy in stem cell transplantation therapy.

Transl Stroke Res 2013, 4:76-88. PubMedAbstract | PublisherFullText

Rais Y, Zviran A, Geula S, Gafni O, Chomsky E, Viukov S, et al.: Deterministic direct reprogramming of somatic cells to pluripotency.

Nature 2013, 502:65-70. PubMedAbstract | PublisherFullText

Riggs JW, Barrilleaux BL, Varlakhanova N, Bush KM, Chan V, Knoepfler PS: Induced pluripotency and oncogenic transformation are related processes.

Stem Cells Dev 2013, 22:37-50. PubMedAbstract | PublisherFullText

Christoforou N, Liau B, Chakraborty S, Chellapan M, Bursac N, Leong KW: Induced pluripotent stem cell-derived cardiac progenitors differentiate to cardiomyocytes and form biosynthetic tissues.

PLoS One 2013, 8:e65963. PubMedAbstract | PublisherFullText

Fisher MB, Mauck RL: Tissue engineering and regenerative medicine: recent innovations and the transition to translation.

Tissue Eng Part B Rev 2013, 19:1-13. PubMedAbstract | PublisherFullText

Beltrami AP, Urbanek K, Kajstura J, Yan SM, Finato N, Bussani R, et al.: Evidence that human cardiac myocytes divide after myocardial infarction.

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Challenges in identifying the best source of stem cells ...

Cardiac Stem Cells Comments Off on Challenges in identifying the best source of stem cells … | October 26th, 2015

Endogenous cardiac stem cells (eCSCs) are tissue-specific stem progenitor cells harboured within the adult mammalian heart.

They were first discovered in 2003 by Bernardo Nadal-Ginard, Piero Anversa and colleagues [1][2] in the adult rat heart and since then have been identified and isolated from mouse, dog, porcine and human hearts.[3][4]

The adult heart was previously thought to be a post mitotic organ without any regenerative capability. The identification of eCSCs has provided an explanation for the hitherto unexplained existence of a subpopulation of immature cycling myocytes in the adult myocardium. Indeed, recent evidence from a genetic fate-mapping study established that stem cells replenish adult mammalian cardiomyocytes lost by cardiac wear and tear and injury throughout the adult life.[5] Moreover, it is now accepted that myocyte death and myocyte renewal are the two sides of the proverbial coin of cardiac homeostasis in which the eCSCs play a central role.[6] These findings produced a paradigm shift in cardiac biology and opened new opportunities and approaches for future treatment of cardiac diseases by placing the heart squarely amongst other organs with regenerative potential such as the liver, skin, muscle, CNS. However, they have not changed the well-established fact that the working myocardium is mainly constituted of terminally differentiated contractile myocytes. This fact does not exclude, but is it fully compatible with the heart being endowed with a robust intrinsic regenerative capacity which resides in the presence of the eCSCs throughout the individual lifespan.

Briefly, eCSCs have been first identified through the expression of c-kit, the receptor of the stem cell factor and the absence of common hematopoietic markers, like CD45. Afterwards, different membrane markers (Sca-1, Abcg-2, Flk-1) and transcription factors (Isl-1, Nkx2.5, GATA4) have been employed to identify and characterize these cells in the embryonic and adult life.[7] eCSCs are clonogenic, self renewing and multipotent in vitro and in vivo,[8] capable of generating the 3 major cell types of the myocardium: myocytes, smooth muscle and endothelial vascular cells.[9] They express several markers of stemness (i.e. Oct3/4, Bmi-1, Nanog) and have significant regenerative potential in vivo.[10] When cloned in suspension they form cardiospheres,[11] which when cultured in a myogenic differentiation medium, attach and differentiate into beating cardiomyocytes.

In 2012, it was proposed that Isl-1 is not a marker for endogenous cardiac stem cells.[12] That same year, a different group demonstrated that Isl-1 is not restricted to second heart field progenitors in the developing heart, but also labels cardiac neural crest.[13] It has also been reported that Flk-1 is not a specific marker for endogenous and mouse ESC-derived Isl1+ CPCs. While some eCSC discoveries have been brought into question, there has been success with other membrane markers. For instance, it was demonstrated that the combination of Flt1+/Flt4+ membrane markers identifies an Isl1+/Nkx2.5+ cell population in the developing heart. It was also shown that endogenous Flt1+/Flt4+ cells could be expanded in vitro and displayed trilineage differentiation potential. Flt1+/Flt4+ CPCs derived from iPSCs were shown to engraft into the adult myocardium and robustly differentiate into cardiomyocytes with phenotypic and electrophysiologic characteristics of adult cardiomyocytes.[14]

With the myocardium now recognized as a tissue with limited regenerating potential,[15] harbouring eCSCs that can be isolated and amplified in vitro [16] for regenerative protocols of cell transplantation or stimulated to replicate and differentiate in situ in response to growth factors,[17] it has become reasonable to exploit this endogenous regenerative potential to replace lost/damaged cardiac muscle with autologous functional myocardium.

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Endogenous cardiac stem cell - Wikipedia, the free ...

Cardiac Stem Cells Comments Off on Endogenous cardiac stem cell – Wikipedia, the free … | October 23rd, 2015

An isolated cardiac muscle cell, beating

Cardiac muscle (heart muscle) is involuntary striated muscle that is found in the walls and histological foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle. These three types of muscle all form in the process of myogenesis. The cells that constitute cardiac muscle, called cardiomyocytes or myocardiocytes, contain only three nuclei.[1][2][pageneeded] The myocardium is the muscle tissue of the heart, and forms a thick middle layer between the outer epicardium layer and the inner endocardium layer.

Coordinated contractions of cardiac muscle cells in the heart propel blood out of the atria and ventricles to the blood vessels of the left/body/systemic and right/lungs/pulmonary circulatory systems. This complex mechanism illustrates systole of the heart.

Cardiac muscle cells, unlike most other tissues in the body, rely on an available blood and electrical supply to deliver oxygen and nutrients and remove waste products such as carbon dioxide. The coronary arteries help fulfill this function.

Cardiac muscle has cross striations formed by rotating segments of thick and thin protein filaments. Like skeletal muscle, the primary structural proteins of cardiac muscle are myosin and actin. The actin filaments are thin, causing the lighter appearance of the I bands in striated muscle, whereas the myosin filament is thicker, lending a darker appearance to the alternating A bands as observed with electron microscopy. However, in contrast to skeletal muscle, cardiac muscle cells are typically branch-like instead of linear.

Another histological difference between cardiac muscle and skeletal muscle is that the T-tubules in the cardiac muscle are bigger and wider and track laterally to the Z-discs. There are fewer T-tubules in comparison with skeletal muscle. The diad is a structure in the cardiac myocyte located at the sarcomere Z-line. It is composed of a single T-tubule paired with a terminal cisterna of the sarcoplasmic reticulum. The diad plays an important role in excitation-contraction coupling by juxtaposing an inlet for the action potential near a source of Ca2+ ions. This way, the wave of depolarization can be coupled to calcium-mediated cardiac muscle contraction via the sliding filament mechanism. Cardiac muscle forms these instead of the triads formed between the sarcoplasmic reticulum in skeletal muscle and T-tubules. T-tubules play critical role in excitation-contraction coupling (ECC). Recently, the action potentials of T-tubules were recorded optically by Guixue Bu et al.[3]

The cardiac syncytium is a network of cardiomyocytes connected to each other by intercalated discs that enable the rapid transmission of electrical impulses through the network, enabling the syncytium to act in a coordinated contraction of the myocardium. There is an atrial syncytium and a ventricular syncytium that are connected by cardiac connection fibres.[4] Electrical resistance through intercalated discs is very low, thus allowing free diffusion of ions. The ease of ion movement along cardiac muscle fibers axes is such that action potentials are able to travel from one cardiac muscle cell to the next, facing only slight resistance. Each syncyntium obeys the all or none law.[5]

Intercalated discs are complex adhering structures that connect the single cardiomyocytes to an electrochemical syncytium (in contrast to the skeletal muscle, which becomes a multicellular syncytium during mammalian embryonic development). The discs are responsible mainly for force transmission during muscle contraction. Intercalated discs are described to consist of three different types of cell-cell junctions: the actin filament anchoring adherens junctions, the intermediate filament anchoring desmosomes , and gap junctions. They allow action potentials to spread between cardiac cells by permitting the passage of ions between cells, producing depolarization of the heart muscle. However, novel molecular biological and comprehensive studies unequivocally showed that intercalated discs consist for the most part of mixed-type adhering junctions named area composita (pl. areae compositae) representing an amalgamation of typical desmosomal and fascia adhaerens proteins (in contrast to various epithelia).[6][7][8] The authors discuss the high importance of these findings for the understanding of inherited cardiomyopathies (such as arrhythmogenic right ventricular cardiomyopathy).

Under light microscopy, intercalated discs appear as thin, typically dark-staining lines dividing adjacent cardiac muscle cells. The intercalated discs run perpendicular to the direction of muscle fibers. Under electron microscopy, an intercalated disc's path appears more complex. At low magnification, this may appear as a convoluted electron dense structure overlying the location of the obscured Z-line. At high magnification, the intercalated disc's path appears even more convoluted, with both longitudinal and transverse areas appearing in longitudinal section.[9]

In contrast to skeletal muscle, cardiac muscle requires extracellular calcium ions for contraction to occur. Like skeletal muscle, the initiation and upshoot of the action potential in ventricular cardiomyocytes is derived from the entry of sodium ions across the sarcolemma in a regenerative process. However, an inward flux of extracellular calcium ions through L-type calcium channels sustains the depolarization of cardiac muscle cells for a longer duration. The reason for the calcium dependence is due to the mechanism of calcium-induced calcium release (CICR) from the sarcoplasmic reticulum that must occur during normal excitation-contraction (EC) coupling to cause contraction. Once the intracellular concentration of calcium increases, calcium ions bind to the protein troponin, which allows myosin to bind to actin and contraction to occur.

Until recently, it was commonly believed that cardiac muscle cells could not be regenerated. However, a study reported in the April 3, 2009 issue of Science contradicts that belief.[10] Olaf Bergmann and his colleagues at the Karolinska Institute in Stockholm tested samples of heart muscle from people born before 1955 who had very little cardiac muscle around their heart, many showing with disabilities from this abnormality. By using DNA samples from many hearts, the researchers estimated that a 20-year-old renews about 1% of heart muscle cells per year, and about 45 percent of the heart muscle cells of a 50-year-old were generated after he or she was born.

One way that cardiomyocyte regeneration occurs is through the division of pre-existing cardiomyocytes during the normal aging process.[11] The division process of pre-existing cardiomyocytes has also been shown to increase in areas adjacent to sites of myocardial injury. In addition, certain growth factors promote the self-renewal of endogenous cardiomyocytes and cardiac stem cells. For example, insulin-like growth factor 1, hepatocyte growth factor, and high-mobility group protein B1 increase cardiac stem cell migration to the affected area, as well as the proliferation and survival of these cells.[12] Some members of the fibroblast growth factor family also induce cell-cycle re-entry of small cardiomyocytes. Vascular endothelial growth factor also plays an important role in the recruitment of native cardiac cells to an infarct site in addition to its angiogenic effect.

Based on the natural role of stem cells in cardiomyocyte regeneration, researchers and clinicians are increasingly interested in using these cells to induce regeneration of damaged tissue. Various stem cell lineages have been shown to be able to differentiate into cardiomyocytes, including bone marrow stem cells. For example, in one study, researchers transplanted bone marrow cells, which included a population of stem cells, adjacent to an infarct site in a mouse model. Nine days after surgery, the researchers found a new band of regenerating myocardium.[13] However, this regeneration was not observed when the injected population of cells was devoid of stem cells, which strongly suggests that it was the stem cell population that contributed to the myocardium regeneration. Other clinical trials have shown that autologous bone marrow cell transplants delivered via the infarct-related artery decreases the infarct area compared to patients not given the cell therapy.[14]

Occlusion (blockage) of the coronary arteries by atherosclerosis and/or thrombosis can lead to myocardial infarction (heart attack), where part of the myocardium is injured due to ischemia (not receiving enough oxygen). This occurs because coronary arteries are functional end arteries - i.e. there is almost no overlap in the areas supplied by different arteries (anastomoses) so that if one fails, others cannot adequately perfuse the region, unlike in other tissues.

Certain viruses lead to myocarditis (inflammation of the myocardium). Cardiomyopathies are inherent diseases of the myocardium, many of which are caused by genetic mutations.

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