In the early 1980s, when the transplant act was written, the process was more demanding, involving anesthesia and the use of large, hollow needles to extract marrow from a donors hip. But today, more than two-thirds of marrow donations are done via apheresis. Blood is taken from a donors arm, the bone-marrow stem cells are filtered out, and the blood is then returned to the donor through a needle in the other arm.

The Ninth Circuit panel held that these filtered stem cells are merely components of blood no different from blood-derived plasma, platelets and clotting factors, for which donor compensation is allowed.

The strongest opposition to compensation comes from the National Marrow Donor Program, the Minneapolis-based nonprofit that maintains the nations largest donor registry. Michael Boo, the programs chief strategy officer, says of reimbursement, Is that what we want people to be motivated by?

The problem with this logic is that altruism has proven insufficient to motivate enough people to give marrow and, as a result, people die.

HHS is presumably under pressure from the National Marrow Donor Program. The department does not otherwise explain its proposed rule except to claim that compensation runs afoul of the transplant acts intent to ban commodification of human stem cells and to curb opportunities for coercion and exploitation, encourage altruistic donation and decrease the likelihood of disease transmission.

But how could such concerns plausibly apply to marrow stem cells and not to blood plasma? The process of collecting plasma is safe: No serious infection has been transmitted in plasma-derived products in nearly two decades, according to the Plasma Protein Therapeutics Association. Strenuous screening and testing in a robust regulatory environment, coupled with voluntary industry standards and sophisticated manufacturing processes, have created what has been called the safest blood product available today.

Constitutional violation

Outlawing compensation for stem blood cells but not mature blood cells might even violate the constitutional guarantee of equal protection of the law, according to Jeff Rowes, a lawyer at the Institute for Justice, which represented Flynn.

HHS should withdraw its proposal. Ideally, Congress should thwart future regulatory mischief by amending the National Organ Transplant Act to stipulate that marrow stem cells are not organs.

Each year, 2,000 to 3,000 Americans in need of marrow transplants die waiting for a match. Altruism is a virtue, but clearly it is not a dependable motive for marrow donation.

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Dr. Hans-Willem Snoeck and colleagues at Columbia University Medical Center reported the first successful development of functional human lung tissue from stem cells in the Dec. 1, 2013, edition of the journal Nature Biotechnology.

The development is an extension of Snoecks previous work in producing human induced pluripotent stem cells from skin cells. Human induced pluripotent stem cells perform exactly like human embryonic stem cells. The benefits of human induced pluripotent stem cells from include the avoidance of potential rejection and legal complications.

The researchers were able to create the six most necessary lung tissues from induced pluripotent stem cells. The work included the development of type 2 alveolar epithelial cells that are necessary to produce surfactants that facilitate the exchange of oxygen and carbon dioxide in the lungs.

The development indicates that lung transplants from donors will eventually become a thing of the past as skin cells from a person with a lung disease can be turned into stem cells that can develop an entire new lung. This method avoids any chance of rejection because the lungs developed from the skin cells are the same as lung cells that a person was born with.

The development also will enable selected cell regeneration of lung cells to treat specific diseases that only involve certain parts of the lung.

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[International version] Linda van Laake: "We want to work together to improve stem cell treatment"
Dr Linda van Laake is assistant professor and specialist registrar in Cardiology at the University Medical Center Utrecht and Hubrecht Institute. She carries...

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[International version] Linda van Laake: "We want to work together to improve stem cell treatment" - Video

Finished heart switches stem cells off

Transcription factor Ajuba regulates stem cell activity in the heart during embryonic development

July 12, 2012

It is not unusual for babies to be born with congenital heart defects. This is because the development of the heart in the embryo is a process which is not only extremely complex, but also error-prone. Scientists from the Max Planck Institute for Heart and Lung Research in Bad Nauheim have now identified a key molecule that plays a central role in regulating the function of stem cells in the heart. As a result, not only could congenital heart defects be avoided in future, but new ways of stimulating the regeneration of damaged hearts in adults may be opened up.

Cardiac development out of control: Absence of the transcription factor Ajuba during cardiac development, as is the case in the right-hand photo due to genetic intervention, disrupts development of the heart in the fish embryo. In addition to an increased number of cardiac muscle cells (green with red-stained nuclei), the heart is additionally deformed during development.

Max Planck Institute for Heart and Lung Research

Max Planck Institute for Heart and Lung Research

It's a long road from a cluster of cells to a finished heart. Cell division transforms what starts out as a collection of only a few cardiac stem cells into an ever-larger structure from which the various parts of the heart, such as ventricles, atria, valves and coronary vessels, develop. This involves the stem and precursor cells undergoing a complex process which, in addition to tightly regulated cell division, also includes cell migration, differentiation and specialisation. Once the heart is complete, the stem cells are finally switched off.

Scientists from the Max Planck Institute for Heart and Lung Research in Bad Nauheim have now discovered how major parts of this development process are regulated. Their search initially focused on finding binding partners for transcription factor Isl1. Isl1 is characteristic of a specific group of cardiac stem cells which are consequently also known as Isl1+ cells. During their search, the researchers came across Ajuba, a transcription factor from the group of LIM proteins. "We then took a closer a look at the interaction between these two molecules and came to the conclusion that Ajuba must be an important switch", says Gergana Dobreva, head of the "Origin of Cardiac Cell Lineages" Research Group at the Bad Nauheim-based Max Planck Institute.

Using an animal model, the scientists then investigated the effects of a defective switch on cardiac development. Embryonic development can be investigated particularly effectively in the zebrafish. The Bad Nauheim-based researchers therefore produced a genetically modified fish that lacked a functioning Ajuba protein. Cardiac development in these fishes was in fact severely disrupted. In addition to deformation of the heart, caused by twisting of the cardiac axis, what particularly struck the researchers was a difference in size in comparison with control animals. "In almost all the investigated fish we observed a dramatic enlargement of the heart. If Ajuba is absent, there is clearly no other switch that finally silences the Isl1-controlled part of cardiac development", says Dobreva.

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Skin Doctors YouthCell Range Sophie Falkiner TVC
YouthCell contains the latest plant stem cell technology (PhytoCellTec) to help delay the appearance of chronological ageing of the skin. These plant stem ...

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Scientists have developed a breakthrough technique to grow artificial skin - using stem cells taken from the umbilical cord. The new method means major burn patients could benefit from faster skin grafting, the researchers say, as the artificial skin can be stored and used when needed.

According to the World Health Organization (WHO), there were approximately 410,000 burn injuries in the US in 2008, of which around 40,000 required hospitalization.

Patients who have suffered severe burns may require skin grafts. At present, this involves the growth of artificial skin using healthy skin from the patients' own bodies. But the researchers note this process can take weeks.

"Creating this new type of skin using stem cells, which can be stored in tissue banks, means that it can be used instantly when injuries are caused, and which would bring the application of artificial skin forward many weeks," says study author Antonio Campos, professor of histology at the University of Granada in Spain.

To create the new technique, details of which are published in the journal Stem Cells Translational Medicine, the scientists used Wharton jelly mesenschymal stem cells from the human umbilical cord.

Previous research from the team had already led them to believe that stem cells from the umbilical cord could be turned into epithelia cells (tissue cells).

The investigators note that the stem cells are "excellent candidates" for tissue engineering due to their "proliferation and differentiation capabilities," but that their potential to turn into epithelial cells had not been explored, until now.

The scientists combined the umbilical cord stem cells with a biomaterial made of fibrin - a protein found in the clotting of blood - and agarose - a polymer usually extracted from seaweed.

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Stem Cell Therapy Injections
Stem Cell therapy, is one form of Comprehensive Prolotherapy available for arthritis treatment, and other chronic pain conditions at Caring Medical and Rehab...

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Stem Cell Treatment at Your Fingertips Stem cell therapy has come a long way over the last ten years, despite repeated interventions by some western governments to restrict its research. One place which has not suffered from these setbacks is China.

At our facilities in Beijing, we have been administering treatments using fetal stem cells for nearly ten years with ever improving results. Our sophisticated stem cell treatment techniques and experience ensure patients receive the highest quality therapy in the world and an alternative to existing treatments that they cannot find in their own country.

We use the strictest protocols to ensure that all our stem cells are disease-free and healthy. Most of our doctors were educated in the West and have a strong understanding of the demands of western patients.

We believe people should not have to put up with their illness when an alternative already exists. Our mission is to improve the quality of life of all our patients and enable you to gain control over your life.

View our Current Treatments section to find out more about the stem cell treatment and therapy we can provide you with.

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Stem Cell Treatment and Stem Cell Therapy | Vista Stem Cell

Charles A. Goldthwaite, Jr., Ph.D.

Cardiovascular disease (CVD), which includes hypertension, coronary heart disease (CHD), stroke, and congestive heart failure (CHF), has ranked as the number one cause of death in the United States every year since 1900 except 1918, when the nation struggled with an influenza epidemic.1 In 2002, CVD claimed roughly as many lives as cancer, chronic lower respiratory diseases, accidents, diabetes mellitus, influenza, and pneumonia combined. According to data from the 19992002 National Health and Nutrition Examination Survey (NHANES), CVD caused approximately 1.4 million deaths (38.0 percent of all deaths) in the U.S. in 2002. Nearly 2600 Americans die of CVD each day, roughly one death every 34 seconds. Moreover, within a year of diagnosis, one in five patients with CHF will die. CVD also creates a growing economic burden; the total health care cost of CVD in 2005 was estimated at $393.5 billion dollars.

Given the aging of the U.S. population and the relatively dramatic recent increases in the prevalence of cardiovascular risk factors such as obesity and type 2 diabetes,2,3 CVD will continue to be a significant health concern well into the 21st century. However, improvements in the acute treatment of heart attacks and an increasing arsenal of drugs have facilitated survival. In the U.S. alone, an estimated 7.1 million people have survived a heart attack, while 4.9 million live with CHF.1 These trends suggest an unmet need for therapies to regenerate or repair damaged cardiac tissue.

Ischemic heart failure occurs when cardiac tissue is deprived of oxygen. When the ischemic insult is severe enough to cause the loss of critical amounts of cardiac muscle cells (cardiomyocytes), this loss initiates a cascade of detrimental events, including formation of a non-contractile scar, ventricular wall thinning (see Figure 6.1), an overload of blood flow and pressure, ventricular remodeling (the overstretching of viable cardiac cells to sustain cardiac output), heart failure, and eventual death.4 Restoring damaged heart muscle tissue, through repair or regeneration, therefore represents a fundamental mechanistic strategy to treat heart failure. However, endogenous repair mechanisms, including the proliferation of cardiomyocytes under conditions of severe blood vessel stress or vessel formation and tissue generation via the migration of bone-marrow-derived stem cells to the site of damage, are in themselves insufficient to restore lost heart muscle tissue (myocardium) or cardiac function.5 Current pharmacologic interventions for heart disease, including beta-blockers, diuretics, and angiotensin-converting enzyme (ACE) inhibitors, and surgical treatment options, such as changing the shape of the left ventricle and implanting assistive devices such as pacemakers or defibrillators, do not restore function to damaged tissue. Moreover, while implantation of mechanical ventricular assist devices can provide long-term improvement in heart function, complications such as infection and blood clots remain problematic.6 Although heart transplantation offers a viable option to replace damaged myocardium in selected individuals, organ availability and transplant rejection complications limit the widespread practical use of this approach.

Figure 6.1. Normal vs. Infarcted Heart. The left ventricle has a thick muscular wall, shown in cross-section in A. After a myocardial infarction (heart attack), heart muscle cells in the left ventricle are deprived of oxygen and die (B), eventually causing the ventricular wall to become thinner (C).

2007 Terese Winslow

The difficulty in regenerating damaged myocardial tissue has led researchers to explore the application of embryonic and adult-derived stem cells for cardiac repair. A number of stem cell types, including embryonic stem (ES) cells, cardiac stem cells that naturally reside within the heart, myoblasts (muscle stem cells), adult bone marrow-derived cells, mesenchymal cells (bone marrow-derived cells that give rise to tissues such as muscle, bone, tendons, ligaments, and adipose tissue), endothelial progenitor cells (cells that give rise to the endothelium, the interior lining of blood vessels), and umbilical cord blood cells, have been investigated to varying extents as possible sources for regenerating damaged myocardium. All have been tested in mouse or rat models, and some have been tested in large animal models such as pigs. Preliminary clinical data for many of these cell types have also been gathered in selected patient populations.

However, clinical trials to date using stem cells to repair damaged cardiac tissue vary in terms of the condition being treated, the method of cell delivery, and the primary outcome measured by the study, thus hampering direct comparisons between trials.7 Some patients who have received stem cells for myocardial repair have reduced cardiac blood flow (myocardial ischemia), while others have more pronounced congestive heart failure and still others are recovering from heart attacks. In some cases, the patient's underlying condition influences the way that the stem cells are delivered to his/her heart (see the section, quot;Methods of Cell Deliveryquot; for details). Even among patients undergoing comparable procedures, the clinical study design can affect the reporting of results. Some studies have focused on safety issues and adverse effects of the transplantation procedures; others have assessed improvements in ventricular function or the delivery of arterial blood. Furthermore, no published trial has directly compared two or more stem cell types, and the transplanted cells may be autologous (i.e., derived from the person on whom they are used) or allogeneic (i.e., originating from another person) in origin. Finally, most of these trials use unlabeled cells, making it difficult for investigators to follow the cells' course through the body after transplantation (see the section quot;Considerations for Using These Stem Cells in the Clinical Settingquot; at the end of this article for more details).

Despite the relative infancy of this field, initial results from the application of stem cells to restore cardiac function have been promising. This article will review the research supporting each of the aforementioned cell types as potential source materials for myocardial regeneration and will conclude with a discussion of general issues that relate to their clinical application.

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6. Mending a Broken Heart: Stem Cells and Cardiac Repair [Stem ...

Nov. 28, 2013 Up until a few years ago, the common school of thought held that the mammalian heart had very little regenerative capacity. However, scientists now know that heart muscle cells constantly regenerate, albeit at a very low rate. Researchers at the Max Planck Institute for Heart and Lung Research in Bad Nauheim, have identified a stem cell population responsible for this regeneration. Hopes are growing that it will be possible in future to stimulate the self-healing powers of patients with diseases and disorders of the heart muscle, and thus develop new potential treatments.

Some vertebrates seem to have found the fountain of youth, the source of eternal youth, at least when it comes to their heart. In many amphibians and fish, for example, this important organ has a marked capacity for regeneration and self-healing. Some species in the two animal groups have even perfected this capability and can completely repair damage caused to heart tissue, thus maintaining the organ's full functionality.

The situation is different for mammals, whose hearts have a very low regenerative capacity. According to the common school of thought that has prevailed until recently, the reason for this deficit is that the heart muscle cells in mammals cease dividing shortly after birth. It was also assumed that the mammalian heart did not have any stem cells that could be used to form new heart muscle cells. On the contrary: new studies show that aged muscle cells are also replaced in mammalian hearts. Experts estimate, however, that between just one and four percent of heart muscle cells are replaced every year.

Scientists in Thomas Braun's Research Group at the Max Planck Institute for Heart and Lung Research have succeeded in identifying a stem cell population in mice that plays a key role in this regeneration of heart muscle cells. Experiments conducted by the researchers in Bad Nauheim on genetically modified mice show that the Sca1 stem cells in a healthy heart are involved in the ongoing replacement of heart muscle cells. The Sca-1 cells increase their activity if the heart is damaged, with the result that significantly more new heart muscle cells are formed.

Since, in comparison to the large amount of heart muscle cells, Sca-1 stem cells account for just a tiny proportion of the cells in the heart muscle, searching for them is like searching for a needle in a haystack. "We also faced the problem that Sca-1 is no longer available in the cells as a marker protein for stem cells after they have been changed into heart muscle cells. To prove this, we had to be inventive," says project leader Shizuka Uchida. The Max Planck researchers genetically modified the stem cells to such an extent that, in addition to the Sca-1, they produced another visible marker. Even if Sca-1 was subsequently no longer visible, the marker could still be detected permanently.

"In this way, we were able to establish that the proportion of heart muscle cells originating from Sca-1 stem cells increased continuously in healthy mice. Around five percent of the heart muscle cells regenerated themselves within 18 months," says Uchida. Moreover, mice suffering from heart disease triggered by the experiment had up to three times more of these newly formed heart muscle cells.

"The data shows that, in principle, the mammalian heart is able to trigger regeneration and renewal processes. Under normal circumstances, however, these processes are not enough to ultimately repair cardiac damage," says Braun. The aim is to find ways in which the formation of new heart muscle cells from heart stem cells can be improved and thereby strengthen the heart's self-healing powers.

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The heart's own stem cells play their part in regeneration

November 28, 2013

By LAURAN NEERGAARD AP Medical Writer

WASHINGTON (AP) -- Could paying for bone marrow cells really boost the number of donors? The Obama administration is taking steps to block a federal court ruling that had opened a way to find out.

Buying or selling organs has long been illegal, punishable by five years in jail. The 1984 National Organ Transplantation Act that set the payment ban didn't just refer to solid organs -- it included bone marrow transplants, too.

Thousands of people with leukemia and other blood diseases are saved each year by bone marrow transplants. Thousands more, particularly minorities, still have trouble finding a genetically compatible match even though millions of volunteers have registered as potential donors under the current altruistic system.

A few years ago, the libertarian Institute for Justice sued the government to challenge that system. It argued that more people with rare marrow types might register to donate -- and not back out later if they're found to be a match -- if they had a financial incentive such as a scholarship paid by a nonprofit group.

Ultimately, a panel of the 9th U.S. Circuit Court of Appeals ruled that some, not all, marrow donors could be compensated -- citing a technological reason. Years ago, the only way to get marrow cells was to extract them from inside bone. Today, a majority of donors give marrow-producing cells through a blood-filtering process that's similar to donating blood plasma. Because it's legal to pay plasma donors, the December 2011 court ruling said marrow donors could be paid, too, as long as they give in that newer way.

"They're not even transplanting your bone marrow. They're transplanting these baby blood cells," said Jeff Rowes, an attorney with the Institute for Justice. It represented some families who'd had trouble finding donors, and was pushing for a study of compensation as a next step.

Not so fast, says the Obama administration. The government now has proposed a regulation to keep the ban intact by rewriting some legal definitions to clarify that it covers marrow-producing stem cells no matter how they're derived.

"It is not a matter of how you obtain it," said Shelley Grant of the Health Resources and Services Administration's transplant division. "Whether we obtain them through the marrow or the circulatory system, it is those stem cells that provide a potential cure."

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http://www.CLINICell.com "MENISCUS TEAR alternative with PRP and Stem Cell Therapy"
http://www.CLINICell.com offers the latest alternative treatments with PRP and Stem Cell Therapy for an MENISCUS Tear. Platelet Rich Plasma and Stem Cell treatments can be used as an alternative...

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An experiment conducted by a team of Japanese researchers from the Keio University School of Medicine, offers new hope for patients with spinal cord injuries. They managed to obtain motor functional recovery after injecting neural stem / progenitor cells (NS / PCs ) in mice. It was known for some time that transplantation of neural stem / progenitor cells (NS / PCs ) promotes functional recovery in spinal cord injury, but it was not very clear what is the optimal transplantation site. Therefore, researchers made an experiment in which they injected NS / PCs in four groups of mice in several sites : at the lesion epicenter, caudal and rostral sites; the control group received phosphate buffered saline. It should be noted that all mice included in the study received contusivespinal cord injury at the T10 level.

Dr. Masaya Nakamura of the Department of Orthopedic Surgery at the Keio University School of Medicine, emphasizedthat it is critical to determine the optimal site for transplanting NS / PCs designed to treat spinal cord injury.Previous studies conducted by the same team showed that NS / PCs injected intravenously or intrathecally in non injury sites, did not engraft at the lesion site in sufficient numbers; the researchers observed that instead these NS / PCs were trapped in the lungs or kidney. In this way they concluded that the optimal outcome for transplantation of NS / PCs can be obtained by intralesional application. To determine how effective isintralesional injection, researchers conducted another study on laboratory mice with spinal cord injury. They injected NS / PCstaken from transgenic mice for Venus and luciferase fusion protein, a method that allowed the researchers to track the cells after transplantation by bioluminescence imaging ( BLI ).

Dr. Nakamura explained that wild-type mice received a spinal cord injury at T10 and thatlow and high doses of NS / PCs taken from fetal transgenic mice were administered to four groups of mice; the fifth group received phosphate buffered saline. Researchers reported that all four groups of mice had functional motor recovery while mice in the control group did not. The researchers also mentioned that in all four groups, the photon counts from BLI transplant were similar. In other words, the survival of stem cells was uniform when it was transplanted more than acertain threshold number of cells. However, it seems that there is a difference between rostral and caudal (RC ) sites and lesion epicenter (E ) because brain -derived neurotropic factor expression was higher in RC.This may mean that the microenvironments of the E and RC sites are similarly able to support NS/PCs transplanted during the sub-acute phase of SCI, researchers said.

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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 encyclopedia

Abstract

Cardiovascular disease (CVD) continues to be one of the main causes of death in the western world. A high burden of disease and the high costs for the healthcare systems claim for novel therapeutic strategies besides current conventional medical care. One decade ago first clinical trials addressed stem cell based therapies as a potential alternative therapeutic strategy for myocardial regeneration and repair. Besides bone marrow derived stem cells (BMCs), adult stem cells from adipose or cardiac tissue have been used in current clinical studies with inconsistent results. Although outcomes in terms of safety and feasibility are generally encouraging, functional improvements were mostly disappointingly low and have failed to reach expectations. In the future, new concepts for myocardial regeneration, especially concerning recovery of cardiomyocyte loss, have to be developed. Transplantation of novel stem or progenitor cell populations with true regenerative potential, direct reprogramming of scar tissue into functional myocardium, tissue engineering or stimulation of endogenous cardiac repair by pharmacological agents are conceivable. This review summarizes current evidence of stem cell based regenerative therapies and discusses future strategies to improve functional outcomes.

KEYWORDS : Myocardial infarction, regenerative medicine, stem cells, tissue engineering, reprogramming

In 2009 cardiovascular disease (CVD) still accounted for 32.3% of all deaths in the United States and therefore continues to be one of the main causes of death (1). From 1999 to 2009, the rate of death due to CVD has declined, but nevertheless the burden of disease remains high. Although improved medical care and acute management of myocardial infarction have led to a considerable reduction of early mortality rate survivors are susceptible to an increased prevalence of chronic heart failure as they develop scarring followed by ventricular remodeling despite optimum medical care (2,3).

Interestingly, cardiovascular operations and interventional procedures increased by 28% from 2000 to 2010 implicating an enormous cost factor for the healthcare system (1). For 2009, it was estimated that the direct and indirect costs of CVD and stroke add up to about $312.6 billion in the United States, which was more than for any other diagnostic group (1).

The main issue of current pharmacological, interventional or operative therapies is their disability to compensate the irreversible loss of functional cardiomyocytes (4). Hence, the future challenge of cardiovascular therapies will be the functional regeneration of myocardial contractility by novel concepts, like cell based therapy, tissue engineering or reprogramming of scar fibroblasts (5,6).

After promising preclinical results using adult stem and precursor cells for cardiac regeneration a rapid clinical translation using autologous bone marrow cells (BMCs) in patients was initiated (7,8). In the last few years numerous clinical trials addressing the transplantation of various adult stem cell populations for cardiac regeneration have been performed. Essential characteristics for the selected adult stem cell populations are the potential to proliferate, migrate and the ability to transdifferentiate into various mature cell types (9). Today, different adult stem cell sources like BMCs, myocardium or adipose tissue derived cells were already used in clinical trials. Beside direct intracoronary or intramyocardial transplantation of adult stem cells into the heart mobilization of autologous progenitor cells by administration of different cytokines [i.e., erythropoietin (EPO) or granulocyte colony stimulating factor (G-CSF)] were also evaluated in first clinical trials (summarized in and ,).

Regenerative therapies and cell sources currently administered in clinical trials. Current clinical trials use BMCs, ADRCs or CPCs to regenerate impaired myocardium after ischemic events. Alternatively cytokines like EPO or G-CSF are employed to mobilize ...

Transplantation of adult stem cells-clinical trials mentioned in the text.

Mobilization of adult stem cells-clinical trials mentioned in the text.

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Cardiac regeneration: current therapies—future concepts

New research has shown human neural stem cells could improve blood flow in critical limb ischemia through the growth of new vessels. Critical limb ischemia (CLI) is a disease that severely obstructs arteries and reduces the blood flow to legs and feet. CLI remains an unmet clinical problem and with an ageing population and the rise in type II diabetes, the incidence of CLI is expected to increase.

The study, led by academics in the University of Bristol's School of Clinical Sciences, is published online in the American Heart Association journal Arteriosclerosis, Thrombosis, and Vascular Biology.

Current stem cell therapy trials for the treatment of CLI have revitalised new hope for improving symptoms and prolonging life expectancy. However, there are limitations on the use of autologous cell therapy. The patient's own stem cells are generally invasively harvested from bone marrow or require purification from peripheral blood after cytokine stimulation. Other sources contain so few stem cells that ex vivo expansion through lengthy bespoke Good Manufacturing Practice processes is required. Ultimately, these approaches lead to cells of variable quality and potency that are affected by the patient's age and disease status and lead to inconsistent therapeutic outcomes.

In order to circumvent the problem a team, led by Professor Paolo Madeddu in the Bristol Heart Institute at the University of Bristol, has used a conditionally immortalised clonal human neural stem cell (hNSC) line to treat animal models with limb ischaemia and superimposed diabetes. The CTX cell line, established by stem cell company ReNeuron, is genetically modified to produce genetically and phenotypically stable cell banks.

Results of the new study have shown that CTX treatment effectively improves the recovery from ischaemia through the promotion of the growth of new vessels. The safety of CTX cell treatment is currently being assessed in disabled patients with stroke [PISCES trial, NCT01151124]. As a result, the same cell product is immediately available for starting dose ranging safety and efficacy studies in CLI patients.

Professor Paolo Madeddu, Chair of Experimental Cardiovascular Medicine and Head of Regenerative Medicine Section in the Bristol Heart Institute at the University of Bristol, said: "Currently, there are no effective drug interventions to treat CLI. The consequences are a very poor quality of life, possible major amputation and a life expectancy of less than one year from diagnosis in 50 per cent of all CLI patients.

"Our findings have shown a remarkable advancement towards more effective treatments for CLI and we have also demonstrated the importance of collaborations between universities and industry that can have a social and medical impact."

Dr John Sinden, Chief Scientific Officer of ReNeuron, added: "The novel idea of using neural stem cells to treat vascular disease arose from a chance discussion with Professor Madeddu. The discussion led to a short pilot study with our cells producing very clear data, which then developed into a further eight experiments exploring different variants of the disease model, the product formulation and dose variation.

"The study also explored the cascade of molecular events that produced vascular and muscle recovery. It is a great example of industry and academia working successfully towards the key goal, clinical translation."

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In computer-based text processing and digital typesetting, a non-breaking space, no-break space or non-breakable space (NBSP) is a variant of the space character that prevents an automatic line break (line wrap) at its position. In certain formats (such as HTML), it also prevents the collapsing of multiple consecutive whitespace characters into a single space. The non-breaking space is also known as a hard space or fixed space. In Unicode, it is encoded at U+00A0 no-break space (HTML:    ).

Text-processing software typically assumes that an automatic line break may be inserted anywhere a space character occurs; a non-breaking space prevents this from happening (provided the software recognizes the character). For example, if the text 100 km will not quite fit at the end of a line, the software may insert a line break between 100 and km. To avoid this undesirable behaviour, the editor may choose to use a non-breaking space between 100 and km. This guarantees that the text 100km will not be broken: if it does not fit at the end of a line it is moved in its entirety to the next line.

A second common application of non-breaking spaces is in plain text file formats such as SGML, HTML, TeX, and LaTeX, which sometimes treat sequences of whitespace characters (space, newline, tab, form feed, etc.) as if they were a single white-space character. Such collapsing of white-space allows the author to neatly arrange the source text using line breaks, indentation and other forms of spacing without affecting the final typeset result.[1][2]

In contrast, non-breaking spaces are not merged with neighboring whitespace characters, and can therefore be used by an author to insert additional visible space in the formatted text. For example, in HTML, non-breaking spaces may be used in conjunction with a fixed-width font to create tabular alignment (courier new font family used):

Column 1Column 2 ---------------- 1.22.3

(note that the use of the pre tag, the whitespace:pre CSS rule, or a table are alternative, if not necessarily better, ways to achieve the same result in HTML)

If ordinary spaces are used instead then the spaces are collapsed when the HTML is rendered and the layout is broken:

Column 1 Column 2 -------- -------- 1.2 2.3

Non-breaking space can also be used to automatically change formatting in a document. This is useful for things like class plans and recipe files where the description of a cell or line may be different from the actual text or title.

Unicode defines several other non-break space characters[3] that differ from the regular space in width:

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Artificial skin created using stem cells from umbilical cord ...

Other common name(s): cellular therapy, fresh cell therapy, live cell therapy, glandular therapy, xenotransplant therapy

Scientific/medical name(s): none

In cell therapy, processed tissue from the organs, embryos, or fetuses of animals such as sheep or cows is injected into patients. Cell therapy is promoted as an alternative form of cancer treatment.

Available scientific evidence does not support claims that cell therapy is effective in treating cancer or any other disease. Serious side effects can result from cell therapy. It may in fact be lethalseveral deaths have been reported. It is important to distinguish between this alternative method involving animal cells and mainstream cancer treatments that use human cells, such as bone marrow transplantation.

In cell therapy, live or freeze-dried cells or pieces of cells from the healthy organs, fetuses, or embryos of animals such as sheep or cows are injected into patients. This is supposed to repair cellular damage and heal sick or failing organs. Cell therapy is promoted as an alternative therapy for cancer, arthritis, heart disease, Down syndrome, and Parkinson disease.

Cell therapy is also marketed to counter the effects of aging, reverse degenerative diseases, improve general health, increase vitality and stamina, and enhance sexual function. Some practitioners have proposed using cell therapy to treat AIDS patients.

The theory behind cell therapy is that the healthy animal cells injected into the body can find their way to weak or damaged organs of the same type and stimulate the body's own healing process. The choice of the type of cells to use depends on which organ is having the problem. For instance, a patient with a diseased liver may receive injections of animal liver cells. Most cell therapists today use cells taken from taken from the tissue of animal embryos.

Supporters assert that after the cells are injected into the body, they are transported directly to where they are most needed. They claim that embryonic and fetal animal tissue contains therapeutic agents that can repair damage and stimulate the immune system, thereby helping cells in the body heal.

The alternative treatment cell therapy is very different from some forms of proven therapy that use live human cells. Bone marrow transplants infuse blood stem cellsfrom the patient or a carefully matched donorafter the patients own bone marrow cells have been destroyed. Studies have shown that bone marrow transplants are effective in helping to treat several types of cancer. In another accepted procedure, damaged knee cartilage can be repaired by taking cartilage cells from the patient's knee, carefully growing them in the laboratory, and then injecting them back into the joint. Approaches involving transplants of other types of human stem cells are being studied as a possible way to replace damaged nerve or heart muscle cells, but these approaches are still experimental.

First, healthy live cells are harvested from the organs of juvenile or adult live animals, animal embryos, or animal fetuses. These cells may be taken from the brain, pituitary gland, thyroid gland, thymus gland, liver, kidney, pancreas, spleen, heart, ovaries, testicles, or even from whole embryos. Patients might receive one or several types of animal cells. Some cell therapists inject fresh cells into their patients. Others freeze them first, which kills the cells, and they may filter out some of the cell components. Frozen cell extracts have a longer "shelf life" and can be screened for disease. Fresh cells cannot be screened. A course of cell therapy to address a specific disease might require several injections over a short period of time, whereas cell therapy designed to treat the effects of aging and "increase vitality" may involve injections received over many months.

More here:
Cell Therapy - American Cancer Society

Autism treatment with stem cells
Stem cell therapy for autism treatment in UCTC. Professor Smikodub introduced the method of fetal stem cell therapy on the basis of which autism treatment wa...

By: TheCellTreatment

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Autism treatment with stem cells - Video

http://www.CLINICell.com "ACL TEAR alternative with PRP and Stem Cell Therapy"

By: ClinicellTech

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http://www.CLINICell.com "ACL TEAR alternative with PRP and Stem Cell Therapy" - Video