Enliven: Journal of Anesthesiology and Critical Care Medicine ISSN : 2374 - 4448 I e001
Left Ventricular Assist Device and Resident Cardiac Stem Cells in Heart Failure: Human Heart #39;s Potential Matter.

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Enliven: Journal of Anesthesiology and Critical Care Medicine ISSN : 2374 - 4448 I e001 - Video

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Newswise Hematopoietic stem cells (HSCs) give rise to all blood and immune cells throughout the life of vertebrate organisms, from zebrafish to humans. But details of their genesis remain elusive, hindering efforts to develop induced pluripotent stem cell (iPSC) replacements that might address a host of blood disorders.

In a paper published Nov. 20 in the journal Cell, researchers at the University of California, San Diego School of Medicine describe the surprising and crucial involvement of a pro-inflammatory signaling protein in the creation of HSCs during embryonic development, a finding that could help scientists to finally reproduce HSCs for therapeutic use.

The recent breakthrough of induced pluripotency has made the concept of patient-specific regenerative medicine a reality, said principal investigator David Traver, PhD, professor in the Department of Cellular and Molecular Medicine. The development of some mature cell lineages from iPSCs, such as cardiac and neural, has been reasonably straightforward, but not with HSCs. This is likely due, at least in part, to not fully understanding all of the factors used by the embryo to generate HSCs. We believe the discovery that pro-inflammatory cues are important in vivo will help us recapitulate instruction of HSC fate in vitro from iPSCs.

Traver and colleagues specifically looked at the role of a cytokine (a type of cell signaling protein) called tumor necrosis factor alpha or TNFa, which plays a pivotal role in regulating systemic inflammation and immunity. The work extended previous research by Spanish biologist Victoriano Mulero, who had reported that TNFa was important in the function of the embryonic vascular system and that in animal models where TNF function was absent, blood defects resulted.

The Cell papers first author Raquel Espin-Palazon, a postdoctoral researcher in Travers lab and a former colleague of Muleros, determined that TNFa was required for the emergence of hematopoietic stem cells during embryogenesis in zebrafish a common animal model.

Traver said the finding was completely unexpected because HSCs emerge relatively early in embryonic formation when the developing organism is considered to be largely sterile and devoid of infection.

Thus, there was no expectation that pro-inflammatory signaling would be active at this time or in the blood-forming regions, Traver said. Equally surprising, we found that a population of embryonic myeloid cells, which are transient cells produced before HSCs arise, are the producers of the TNFa needed to establish HSC fate. So it turns out that a small subset of myeloid cells that persist for only a few days in development are necessary to help generate the lineal precursors of the entire adult blood-forming system.

The newly discovered role of TNFa in HSC development mirrors a parallel discovery regarding interferon gamma (INFg), another cytokine and major mediator of pro-inflammatory signaling, highlighting multiple inputs for inflammatory signaling in HSC emergence. Traver said the crucial roles of TNFa and INFg in HSC emergence are likely similar in humans because of the highly conserved nature of HSC development across vertebrate evolution.

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Before There Will Be Blood

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Newswise LA JOLLAResearchers at the Salk Institute have healed injured hearts of living mice by reactivating long dormant molecular machinery found in the animals cells, a finding that could help pave the way to new therapies for heart disorders in humans.

The new results, published November 6 in the journal Cell Stem Cell, suggest that although adult mammals dont normally regenerate damaged tissue, they may retain a latent ability as a holdover from development like their distant ancestors on the evolutionary tree. When the Salk researchers blocked four molecules thought to suppress these programs for regenerating organs, they saw a drastic improvement in heart regeneration and healing in the mice.

The findings provide proof-of-concept for a new type of clinical treatment in the fight against heart disease, which kills about 600,000 people each year in the United Statesmore than AIDS and all cancer types combined, according to the U.S. Centers for Disease Control and Prevention.

Organ regeneration is a fascinating phenomenon that seemingly recapitulates the processes observed during development. However, despite our current understanding of how embryogenesis and development proceeds, the mechanisms preventing regeneration in adult mammals have remained elusive, says the studys senior author Juan Carlos Izpisua Belmonte, a professor in the Gene Expression Laboratory at Salk.

Within the genomes of every cell in our bodies, we have what information we need to generate an organ. Izpisua Belmontes group has for many years focused on elucidating the key molecules involved in embryonic development as well as those potentially underlying healing responses in regenerative organisms such as the zebrafish.

Indeed, back in 2003, Izpisua Belmontes laboratory first identified the signals preceding zebrafish heart regeneration. And in a 2010 Nature paper, the researchers described how regeneration occurred in the zebrafish. Rather than stem cells invading injured heart tissue, the cardiac cells themselves were reverting to a precursor-like state (a process called dedifferentiation), which, in turn, allowed them to proliferate in tissue.

Although in theory it might have seemed like the next logical step to ask whether mammals had evolutionarily conserved any of the right molecular players for this kind of regenerative reprogramming, in practice it was a scientific risk, recalls Ignacio Sancho-Martinez, a postdoctoral researcher in Izpisua Belmontes lab.

When you speak about these things, the first thing that comes to peoples minds is that youre crazy, he says. Its a strange sounding idea, since we associate regeneration with salamanders and fish, but not mammals.

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Salk Scientists Discover a Key to Mending Broken Hearts

Korean stem cells regenerate coach Hiddinks worn-out knee cartilage NOVEMBER 06, 2014 03:02 Korean stem cells regenerate coach Hiddinks worn-out knee cartilage . NOVEMBER 06, 2014 03:02. . Guus Hiddink, the legendary soccer coach who led the Korean national team to the semifinals at the 2002 World Cup Korea-Japan, has been reborn as a figure symbolizing excellence of Korean stem cell treatment. Hiddink, who was suffering from severe arthritis, had his knee cartilage almost completely worn out. Rejecting recommendations to take artificial joint surgery by hospitals in the U.S. and Germany, Hiddink chose to take stem cell treatment in Korea. He started treatment in January this year, and was declared as having fully recovered from the illness 10 months later.

The treatment that gave coach Hiddink a second life is Cartistem, which is made from cord blood stem cells. Cartistem, which was developed by Medipost, a bio venture firm, received product licensure as treatment for knee cartilage that has been damaged due to degenerative conditions and repeated injuries from the Korea Food and Drug Ministry in January 2012. It was the first to receive licensure among stem cell treatments in the world. The treatment is undergoing clinical trials in the U.S. to acquire licensure from the Food and Drug Administration. Despite a highly costly price that is not covered by the national health insurance system, the treatment has been used in more than 1,600 patients thus far.

Stem cell treatments developed in Korea include Hearticellgram, a treatment for cardiac infarction, and Cupistem, a treatment for fistulous opening (a disease that causes holes in tissue between rectums and anus), as well as Cartistem. Hearticellgram and Cupistem use stem cells from tissues of the patients own body. Umbilical cord stem cells and autologous stem cells do not derive from human eggs and hence are free from controversy of bioethics. They are results of steadfast research and investment in stem cells by Korean biotech firms.

In tune with the aging society and a growing number of people with chronic diseases, the bio industry is considered a cash cow industry of the future. Notably, the stem cell sector that treats abnormal bodily organs is the most promising field. Not only bio powerhouses such as the U.S., Japan and the European Union but also China have jumped into the industry. As research on induced pluripotent stem cells (iPS) won the Nobel Prize in physiology and medicine recently, countries worldwide are having mounting interest in the field. The Korean government should create an environment to enable Korean biotech firms to take a leap forward in the global market, by providing generous support for investment and putting in place prompt and predictable licensure and approval process.

The treatment that gave coach Hiddink a second life is Cartistem, which is made from cord blood stem cells. Cartistem, which was developed by Medipost, a bio venture firm, received product licensure as treatment for knee cartilage that has been damaged due to degenerative conditions and repeated injuries from the Korea Food and Drug Ministry in January 2012. It was the first to receive licensure among stem cell treatments in the world. The treatment is undergoing clinical trials in the U.S. to acquire licensure from the Food and Drug Administration. Despite a highly costly price that is not covered by the national health insurance system, the treatment has been used in more than 1,600 patients thus far.

Stem cell treatments developed in Korea include Hearticellgram, a treatment for cardiac infarction, and Cupistem, a treatment for fistulous opening (a disease that causes holes in tissue between rectums and anus), as well as Cartistem. Hearticellgram and Cupistem use stem cells from tissues of the patients own body. Umbilical cord stem cells and autologous stem cells do not derive from human eggs and hence are free from controversy of bioethics. They are results of steadfast research and investment in stem cells by Korean biotech firms.

In tune with the aging society and a growing number of people with chronic diseases, the bio industry is considered a cash cow industry of the future. Notably, the stem cell sector that treats abnormal bodily organs is the most promising field. Not only bio powerhouses such as the U.S., Japan and the European Union but also China have jumped into the industry. As research on induced pluripotent stem cells (iPS) won the Nobel Prize in physiology and medicine recently, countries worldwide are having mounting interest in the field. The Korean government should create an environment to enable Korean biotech firms to take a leap forward in the global market, by providing generous support for investment and putting in place prompt and predictable licensure and approval process.

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Heart Disease

With respect to the heart, stem cells have the ability to not only home into the damaged areas but also to initiate a cascade of biological events which both culminate in healing of the heart muscle. For example, animal studies have demonstrated that stem cell therapy will cause new muscle cells to be formed through stimulation of dormant stem cells that are already inside the heart muscle. In these studies, the administered stem cell also transformed into new heart muscle cells.

At Stem Cell Institute, our stem cell treatment protocol for heart failure involves administration of mesenchymal stem cells harvested from human umbilical cord tissue.

The adult stem cells used to treat heart failure at the Stem Cell Institute come from human umbilical cord tissue (allogeneic mesenchymal). These stem cells are expanded at Medistem Panamas state-of-the-art laboratory.

The mesenchymal stem cells we use are recovered from donated umbilical cords following normal, healthy births. Each mother has her medical history screened and is tested for infectious diseases. Proper consent is received from each family prior to donation.

All umbilical cord-derived stem cells are screened for infectious diseases to International Blood Bank Standards before they are cleared for use in patients.

Approximately 1 in 10 donated umbilical cords pass our rigorous screening process.

Through retrospective analysis of our cases, weve identified proteins and genes that allow us to screen several hundred umbilical cord donations to find the ones that we know are most effective. We only use these cells and we call them golden cells.

We go through a very high throughput screening process to find cells that we know have the best anti-inflammatory activity, the best immune modulating capacity, and the best ability to stimulate regeneration.

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Stem Cell Therapy || Heart Failure || Stem Cell Treatment ...

Using stem cells to repair damaged heart muscle in patients with chronic heart failure is safe and beneficial, whether the cells come from patients own bone marrow or from a healthy volunteer, according to a preliminary study by researchers at the Johns Hopkins University School of Medicine and the University of Miami Miller School of Medicine. In a study of 31 patients, the therapy reduced heart muscle scar tissue and improved their quality of life. For many patients in the study, the therapy also enhanced their hearts pumping ability.

An article describing the study, "Comparison of Allogeneic vs. Autologous Bone Marrow-Derived Mesenchymal Stem Cells Delivered by Transendocardial Injection in Patients with Ischemic Cardiomyopathy," is published in the Journal of the American Medical Association (JAMA) on Nov. 6. Results are scheduled to be presented that same day at the American Heart Association Scientific Sessions in Los Angeles.

The researchers say this is the first study to compare autologous stem cells, which are derived from the patients' own bone marrow, to allogeneic stem cells, taken from the marrow of healthy volunteers, in patients with heart disease. The advantage of using allogeneic cells is the potential for developing an off-the-shelf therapy that could be delivered in a more timely way, rather than requiring a bone marrow biopsy from heart failure patients and waiting for the cells to be processed. Also, stem cells from the patients themselves may not be as robust.

All of the study patients had longstanding ischemic cardiomyopathy - chronic heart failure caused by a prior heart attack that blocked blood flow to the heart and damaged heart muscle. The condition affects about 70 percent of the six million people in the United States who suffer from heart failure.

"The primary focus of our study was to determine the safety of the therapy, specifically within 30 days of the treatment," says Gary Gerstenblith, M.D., professor of medicine at the Johns Hopkins University School of Medicine and co-author of the study. "We found that the treatment was safe and also that many of the patients experienced significant improvement, whether they had received the allogeneic or the autologous stem cells," he says.

Patients in the study were randomly selected to have either their own stem cells or donated cells injected directly into their heart muscle. They were monitored for treatment-associated complications, such as death, heart attack, stroke, hospitalization for worsening heart failure and dangerous heart arrhythmias. All of the patients were still alive 12 months after the treatment.

The researchers were especially interested in learning whether the patients immune system would recognize the allogeneic (donated) stem cells as foreign and mount an immune response to reject the cells. Only 3.7 percent of the patients receiving the donated cells had such a response. The cells were injected into the heart muscle just once during a cardiac catheterization procedure.

The particular cells used for the therapy, mesenchymal stem cells, are less likely to stimulate an immune response and rejection than most other stem cells. They have the ability to repair muscular tissues and to reduce inflammation.

Patients in the allogeneic and autologous groups were further divided according to the doses of the stem cells they received. Three different doses were tested: 20 million cells, 100 million cells and 200 million cells.

"We generally think the more the better, but in fact, the lowest dose of 20 million cells appeared to be the most effective at improving the hearts pumping ability as well as reducing the extent of scar tissue," says Peter Johnston, M.D., assistant professor of medicine at Johns Hopkins and co-author of the study.

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Stem Cell Therapy Safely Repairs Damaged Heart Muscle in ...

2 hours ago A cross section through a histotripsy lesion created in bovine liver tissue with the liquified cellular contents washed out revealing the remaining extracellular matrix. The scale bar represents 5mm. Credit: T.Khoklova/UW

Researchers at the University of Washington have developed a way to use sound to create cellular scaffolding for tissue engineering, a unique approach that could help overcome one of regenerative medicine's significant obstacles. The researchers will present their technique at the 168th meeting of the Acoustical Society of America (ASA), held October 27-31, 2014, at the Indianapolis Marriott Downtown Hotel.

The development of the new technique started with somewhat of a serendipitous discovery. The University of Washington team had been studying boiling histotripsy - a technique that uses millisecond-long bursts of high-intensity ultrasound waves to break apart tissue - as a method to eliminate cancerous tumors by liquefying them with ultrasound waves. After the sound waves destroy the tumors, the body should eliminate them as cellular waste. When the researchers examined these 'decellularized' tissues, however, they were surprised by what the boiling left intact.

"In some of our experiments, we discovered that some of the stromal tissue and vasculature was being left behind," said Yak-Nam Wang, a senior engineer at the University of Washington's Applied Physics Laboratory. "So we had the idea about using this to decellularize tissues for tissue engineering and regenerative medicine."

The structure that remains after decellularizing tissues is known as the extracellular matrix, a fibrous network that provides a scaffold for cells to grow upon. Most other methods for decellularizing tissues and organs involve chemical and enzymatic treatments that can cause damage to the tissues and fibers and takes multiple days. Histrostipsy, on the other hand, offers the possibility of fast decellularization of tissue with minimal damage to the matrix.

"In tissue engineering, one of the holy grails is to develop biomimetic structures so that you can replace tissues with native tissue," Wang said. Stripping away cells from already developed tissue could provide a good candidate for these structures, since the extracellular matrix already acts as the cellular framework for tissue systems, Wang said.

Due to its bare composition, the matrix also induces only a relatively weak immune response from the host. The matrix could then theoretically be fed with stem cells or cells from the same person to effectively re-grow an organ.

"The other thought is that maybe you could just implant the extracellular matrix and then the body itself would self-seed the tissues, if it's just a small patch of tissue that you're replacing," Wang said. "You won't have any immune issues, and because you have this biomimetic scaffold that's closer to the native tissue, healing would be better, and the body would recognize it as normal tissue."

Wang is currently investigating decellularization of kidney and liver tissue from large animals. Future work involves increasing the size of the decellularized tissues and assessing their in-vivo regenerative efficacy.

Explore further: The future of regenerative medicine

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High-intensity sound waves may aid regenerative medicine

12 hours ago Fruit fly larva are used to study stem cells key features. Credit: Wikipedia

The study, performed with fruit flies, describes a gene that determines whether a specialized cell conserves the capacity to become a stem cell again. Unveiling the genetic traits that favour the retention of stem cell properties is crucial for regenerative medicine. Published in Cell Reports, the article is the fruit of collaboration between researchers at IRB Barcelona and CSIC.

One kind of stem cell, those referred to as 'facultative', form parttogether with other cellsof tissues and organs. There is apparently nothing that differentiates these cells from the others. However, they have a very special characteristic, namely they retain the capacity to become stem cells again. This phenomenon is something that happens in the liver, an organ that hosts cells that stimulate tissue growth, thus allowing the regeneration of the organ in the case of a transplant. Knowledge of the underlying mechanism that allows these cells to retain this capacity is a key issue in regenerative medicine.

Headed by Jordi Casanova, research professor at the Instituto de Biologa Molecular de Barcelona (IBMB) of the CSIC and at IRB Barcelona, and by Xavier Franch-Marro, CSIC tenured scientist at the Instituto de Biologa Evolutiva (CSIC-UPF), a study published in the journal Cell Reports reveals a mechanism that could explain this capacity. Working with larval tracheal cells of Drosophila melanogaster, these authors report that the key feature of these cells is that they have not entered the endocycle, a modified cell cycle through which a cell reproduces its genome several times without dividing.

"The function of endocycle in living organisms is not fully understood," comments Xavier Franch-Marro. "One of the theories is that endoreplication contributes to enlarge the cell and confers the production of high amounts of protein". This is the case of almost all larval cells of Drosophila.

The scientists have observed that the cells that enter the endocycle lose the capacity to reactivate as stem cells. "The endocycle is linked to an irreversible change of gene expression in the cell," explains Jordi Casanova, "We have seen that inhibition of endocycle entry confers the cells the capacity to reactivate as stem cells".

Cell entry into the endocycle is associated with the expression of the Fzr gene. The researchers have found that inhibition of this gene prevents this entry, which in turn leads to the conversion of the cell into an adult progenitor that retains the capacity to reactivate as a stem cell. Therefore, this gene acts as a switch that determines whether a cell will enter mitosis (the normal division of a cell) or the endocycle, the latter triggering a totally different genetic program with a distinct outcome regarding the capacity of a cell to reactivate as a stem cell.

Explore further: Autophagy helps fast track stem cell activation

More information: Specification of Differentiated Adult Progenitors via Inhibition of Endocycle Entry in the Drosophila Trachea, Nareg J.-V. Djabrayan, Josefa Cruz, Cristina de Miguel, Xavier Franch-Marro, Jordi Casanova, Cell Reports (2014) DOI: dx.doi.org/10.1016/j.celrep.2014.09.043

In spite of considerable research efforts around the world, we still do not know the determining factors that confer stem cells their main particular features: capacity to self-renew and to divide and proliferate. The scientist ...

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A mechanism that allows a differentiated cell to reactivate as a stem cell revealed

Glossary

Below is a glossary of terms related to stem cell research and clinical trials at the Stem Cell Center. For questions about any of these terms, please call the center at 832-355-9405.

Acute myocardial infarction (AMI)The medical term for a "heart attack."Acute myocardial infarction results from a blockage in one or more of the blood vessels leading to the heart. Damage to the heart muscle results, due to the lack of blood flow.

Adult stem cellAn undifferentiated cell found among differentiated cells in a tissue or organ.Thestemcellcan renew itself and change to yield all the specialized cell types of the tissue or organ.

AkinesiaA lack of myocardial wall motion.

AllogeneicA graft or tissue from someone other than the patient such as a donor or other third-party source.

Angina or angina pectorisChest pain that occurs when diseased blood vessels restrict blood flow to the heart.

AngiogenesisA new blood vessel growth.

AngiographyAn x-raytechniqueinwhichdye is injected into the chambers of your heart or the arteries that lead to your heart (the coronary arteries). The test lets doctors measure the blood flow and blood pressure in the heart chambers and see if the coronary arteries are blocked.

AngioplastyA nonsurgical technique for treating diseased arteries by temporarily inflating a tiny balloon inside an artery.

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Stem Cell Education Center - Texas Heart Institute at St ...

KYOTO A team of Japanese researchers has successfully created cardiac tissue sheets generated from human induced pluripotent stem cells, according to a study in the online British journal Scientific Reports.

The team said it is the first time iPS cells have produced an integrated cardiac tissue sheet that includes vascular cells as well as cardiac muscle cells and is close to real tissue in structure.

The stem cell team, led by Kyoto University professor Jun Yamashita, hopes the achievement will contribute to the development of new treatments for heart disease, because it has already found evidence that transplanting the sheets into mice with failing hearts improves in their cardiac condition.

The team used a protein called VEGF, which is related to the growth of blood vessels, as a replacement for the Dkk1 protein previously used to create cardiac muscle sheets from iPS cells.

As a result, iPS cells were simultaneously differentiated to become cardiac muscle cells, vascular mural cells, and the endothelial cells that line the interior surface of blood vessels. The cells were cultivated into a sheet about 1 cm in diameter.

Three-layer cardiac tissue sheets were then transplanted into nine mice with dead or damaged heart muscle caused by heart attacks. In four of the mice, blood vessels formed in the area where the sheets were transplanted, leading to improved cardiac function.

The weak point of iPS cells is that there is a risk of developing cancer, but the cells did not become cancerous within two months of transplantation, the team said.

About 72 percent of the cardiac tissue sheet was made of cardiac muscle cells, while 26 percent of it consisted of endothelial cells as well as vascular mural cells. But the sheet contained a small portion of cells that had not changed, leading the team to call attention to the possibility that a cancerous change might take place over the longer term.

Yamashita said in the study that he believed the new form of cardiac sheets attached well.

Oxygen and nourishment were able to reach cardiac muscle through blood because there were blood vessels, he said.

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Japanese team develops cardiac tissue sheet from human iPS cells

KYOTO A team of Japanese researchers has successfully created cardiac tissue sheets generated from human induced pluripotent stem cells, according to a study in the online British journal Scientific Reports.

The team said it is the first time iPS cells have produced an integrated cardiac tissue sheet that includes vascular cells as well as cardiac muscle cells and is close to real tissue in structure.

The stem cell team, led by Kyoto University professor Jun Yamashita, hopes the achievement will contribute to the development of new treatments for heart disease, because it has already found evidence that transplanting the sheets into mice with failing hearts improves in their cardiac condition.

The team used a protein called VEGF, which is related to the growth of blood vessels, as a replacement for the Dkk1 protein previously used to create cardiac muscle sheets from iPS cells.

As a result, iPS cells were simultaneously differentiated to become cardiac muscle cells, vascular mural cells, and the endothelial cells that line the interior surface of blood vessels. The cells were cultivated into a sheet about 1 cm in diameter.

Three-layer cardiac tissue sheets were then transplanted into nine mice with dead or damaged heart muscle caused by heart attacks. In four of the mice, blood vessels formed in the area where the sheets were transplanted, leading to improved cardiac function.

The weak point of iPS cells is that there is a risk of developing cancer, but the cells did not become cancerous within two months of transplantation, the team said.

About 72 percent of the cardiac tissue sheet was made of cardiac muscle cells, while 26 percent of it consisted of endothelial cells as well as vascular mural cells. But the sheet contained a small portion of cells that had not changed, leading the team to call attention to the possibility that a cancerous change might take place over the longer term.

Yamashita said in the study that he believed the new form of cardiac sheets attached well.

Oxygen and nourishment were able to reach cardiac muscle through blood because there were blood vessels, he said.

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Volume 9, Issue 1 Summary

A groundbreaking study on repairing damaged heart tissue through stem cell therapy has given patients hope that they may again live active lives. An international team of Mayo Clinic researchers and collaborators has done it by discovering a way to regenerate heart tissue.

Clinical trial participant Miroslav Dlacic near his home in Belgrade.

Andre Terzic, M.D., Ph.D., is the Michael S. and Mary Sue Shannon Family Director, Center for Regenerative Medicine, and the Marriott Family Professor of Cardiovascular Diseases Research at Mayo Clinic in Minnesota.

Miroslav Dlacic's heart attack changed his life drastically and seemingly forever. His damaged heart made him too tired to work in his garden or to spend much time at his leather-accessories workshop in Belgrade, Serbia. Like many patients with heart problems, Dlacic, who is 71, thought he would live his remaining years in a weakened condition.

Then, a groundbreaking Mayo Clinic trial of stem cell therapy to repair damaged heart tissue changed his life again this time for the better.

Dlacic agreed to participate in the Mayo Clinic stem cell trial through the hospital in Serbia where he is treated. Two years later, Dlacic is able to walk again without becoming worn out.

"I am more active, more peppy," he says. "I feel quite well."

"It's a paradigm shift," says Andre Terzic, M.D., Ph.D., director of Mayo Clinic's Center for Regenerative Medicine and senior investigator of the stem cell trial. "We are moving from traditional medicine, which addresses the symptoms of disease, to being legitimately able to cure disease."

For decades, treating patients with cardiac disease has typically involved managing heart damage with medication. It's a bit like driving a car without fixing a sluggish engine you manage the consequences as best you can and learn to live with them.

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Regenerating heart tissue through stem cell therapy ...

Category: Science & Technology Posted: October 3, 2014 01:55PM Author: Guest_Jim_*

Heart attacks are pretty serious and something very hard to recover from, in part because heart cells do not multiply and there are few cardiac muscle stem cells to repair the damage. Cardiac patches have been created to replace damaged cells, but because of how they are made, these patches can cause their own health problems. Researchers at Tel Aviv University have recently developed a new hybrid patch that could address those problems.

Traditionally the patches are made by growing cardiac tissue on a collagen scaffold from pig hearts. One of the problems with this approach is the potential for antigens that will trigger an immune response, causing the patient's body to attack the patch. To get around this the researchers instead harvest fatty tissue from the patient's stomach, as the body will not attack its own cells. This left an issue with connectivity, as the cells in the patch must respond to the electrical signals of the heart, and engineered patches do not immediately form the necessary connections. The solution the researchers tried was to deposit gold nanoparticles onto the cardiac tissue, providing the needed conductivity.

So far the nonimmunogenic hybrid patch has shown itself to transfer electrical signals faster and more efficiently than scaffolds without the gold nanoparticles, when tested in animals. The next step for the technology is to test it in larger animals, and eventually perform clinical trials.

Source: American Friends of Tel Aviv University

Link:
Gold Nanoparticles Used to Improve Cardiac Patches

Stem Cell Therapy: Helping the Body Heal Itself

Stem cells are natures own transformers. When the body is injured, stem cells travel the scene of the accident. Some come from the bone marrow, a modest number of others, from the heart itself. Additionally, theyre not all the same. There, they may help heal damaged tissue. They do this by secreting local hormones to rescue damaged heart cells and occasionally turning into heart muscle cells themselves. Stem cells do a fairly good job. But they could do better for some reason, the heart stops signaling for heart cells after only a week or so after the damage has occurred, leaving the repair job mostly undone. The partially repaired tissue becomes a burden to the heart, forcing it to work harder and less efficiently, leading to heart failure.

Initial research used a patients own stem cells, derived from the bone marrow, mainly because they were readily available and had worked in animal studies. Careful study revealed only a very modest benefit, so researchers have moved on to evaluate more promising approaches, including:

No matter what you may read, stem cell therapy for damaged hearts has yet to be proven fully safe and beneficial. It is important to know that many patients are not receiving the most current and optimal therapies available for their heart failure. If you have heart failure, and wondering about treatment options, an evaluation or a second opinion at a Center of Excellence can be worthwhile.

Randomized clinical trials evaluating these different approaches typically allow enrollment of only a few patients from each hospital, and hence what may be available at the Cleveland Clinic varies from time to time. To inquire about current trials, please call 866-289-6911 and speak to our Resource Nurses.

Cleveland Clinic is a large referral center for advanced heart disease and heart failure we offer a wide range of therapies including medications, devices and surgery. Patients will be evaluated for the treatments that best address their condition. Whether patients meet the criteria for stem cell therapy or not, they will be offered the most advanced array of treatment options.

Allogenic: from one person to another (for example: organ transplant)

Autogenic: use of one's own tissue

Myoblasts: immature muscle cells, may be able to change into functioning heart muscle cells

Stem Cells: cells that have the ability to reproduce, generate new cells, and send signals to promote healing

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Stem-Cell Therapy and Repair after Heart Attack and Heart ...

Freeport, Grand Bahama (PRWEB) October 02, 2014

Dr. Todd K. Malan, M.D., presented to the Grand Bahama Medical & Dental Association 14th Annual Scientific Educational Conference on the science, safety and efficacy of adipose- (fat) derived stem and regenerative cells (ADRCs) for ischemic heart disease and other unmet healthcare needs.

"It was an honor to participate in this conference with medical leadership that values this technology and works so tirelessly to serve the people of Grand Bahama," said Dr. Todd Malan." It is an opportunity for us to work closely with local doctors to improve the quality and standards of care for all patients."

Dr. Malan explained the interrelationship between tissue ischemia, inflammation, autoimmune response and cell death and how ADRCs have combined mechanisms known to assist in repairing multi-factorial illnesses associated with those issues.

According to Malan,The procedure begins with the extraction of a persons body fat, a process done using advanced water-assisted liposuction technology. The persons own adult stem cells are then separated from the fat tissue using a European Union-approved cell processing device."

Immediately following this, the cardiologist injects these cells into and around the low blood flow regions of the heart via a cathetera protocol which allows for better targeting of the cells to repair damaged heart tissue.

Adult stem cell therapy for heart disease is emerging as a new alternative for patients with severe heart conditions who want to live a normal life but are restricted in activities they can no longer do.

"As a leader in providing cell therapy, Okyanos is very excited to bring this innovative treatment to patients in a near-shore, regulated jurisdiction with a new standard of care, said Matt Feshbach, CEO of Okyanos. We welcome the opportunity to help those patients with limited options a chance to live a normal life.

Offering this minimally invasive adult stem cell treatment in their new cardiac catherization lab, Okyanos is scheduled to open in October in Freeport, Grand Bahama.

About Okyanos Heart Institute: (Oh key AH nos)

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Okyanos Presents the Science, Safety, and Efficacy of Adult Stem Cell Therapy

Because heart cells cannot multiply and cardiac muscles contain few stem cells, heart tissue is unable to repair itself after a heart attack. Now Tel Aviv University researchers are literally setting a new gold standard in cardiac tissue engineering.

Dr. Tal Dvir and his graduate student Michal Shevach of TAU's Department of Biotechnology, Department of Materials Science and Engineering, and Center for Nanoscience and Nanotechnology, have been developing sophisticated micro- and nanotechnological tools -- ranging in size from one millionth to one billionth of a meter -- to develop functional substitutes for damaged heart tissues. Searching for innovative methods to restore heart function, especially cardiac "patches" that could be transplanted into the body to replace damaged heart tissue, Dr. Dvir literally struck gold. He and his team discovered that gold particles are able to increase the conductivity of biomaterials.

In a study published by Nano Letters, Dr. Dvir's team presented their model for a superior hybrid cardiac patch, which incorporates biomaterial harvested from patients and gold nanoparticles. "Our goal was twofold," said Dr. Dvir. "To engineer tissue that would not trigger an immune response in the patient, and to fabricate a functional patch not beset by signalling or conductivity problems."

A scaffold for heart cells

Cardiac tissue is engineered by allowing cells, taken from the patient or other sources, to grow on a three-dimensional scaffold, similar to the collagen grid that naturally supports the cells in the heart. Over time, the cells come together to form a tissue that generates its own electrical impulses and expands and contracts spontaneously. The tissue can then be surgically implanted as a patch to replace damaged tissue and improve heart function in patients.

According to Dr. Dvir, recent efforts in the scientific world focus on the use of scaffolds from pig hearts to supply the collagen grid, called the extracellular matrix, with the goal of implanting them in human patients. However, due to residual remnants of antigens such as sugar or other molecules, the human patients' immune cells are likely to attack the animal matrix.

In order to address this immunogenic response, Dr. Dvir's group suggested a new approach. Fatty tissue from a patient's own stomach could be easily and quickly harvested, its cells efficiently removed, and the remaining matrix preserved. This scaffold does not provoke an immune response.

Using gold to create a cardiac network

The second dilemma, to establish functional network signals, was complicated by the use of the human extracellular matrix. "Engineered patches do not establish connections immediately," said Dr. Dvir. "Biomaterial harvested for a matrix tends to be insulating and thus disruptive to network signals."

At his Laboratory for Tissue Engineering and Regenerative Medicine, Dr. Dvir explored the integration of gold nanoparticles into cardiac tissue to optimize electrical signaling between cells. "To address our electrical signalling problem, we deposited gold nanoparticles on the surface of our patient-harvested matrix, 'decorating' the biomaterial with conductors," said Dr. Dvir. "The result was that the nonimmunogenic hybrid patch contracted nicely due to the nanoparticles, transferring electrical signals much faster and more efficiently than non-modified scaffolds."

Excerpt from:
A heartbeat away? Hybrid 'patch' could replace transplants

Frankfurt, Germany (PRWEB) September 19, 2014

The Translational Research Institute TRI Medical announced today that its new ND Infusion Catheter is being used in a first-in-man procedure at the University of Frankfurt.

The study commenced on September 4th, 2014 at the University of Frankfurt, Department of Cardiology. The use of the new catheter demonstrated a number of advancements in the delivery of regenerative therapeutics, commonly known as stem cells. We are at the forefront of revolutionizing stem cell delivery to the heart, TRI Medicals Nabil Dib, MD, Msc, offered. The ND Infusion Catheter provides safety and potential efficacy. The catheter also reduces the procedure time to approximately 15 minutes; enabling patients to walk and resume activities in about 2 hours, Dr. Dib continued.

The renowned German Cardiology Center at the University of Frankfurt has extensive experience with the development of cardiac cell-based regenerative therapeutics. Prof. Dr. Andreas M. Zeiher, Chairman of the Department of Cardiology at the University of Frankfurt stated The catheter provides the unique potential to precisely regulate coronary blood flow, while administering cells directly into the heart thus improving safety and potentially efficacy. The innovative design of the catheter's balloon accommodates different vessel sizes, avoiding the need to use multiple catheters, reducing potential risks associated with exchanging the balloon catheter when treating different coronary arteries in an individual patient.

Prior to the first-in-man procedure, extensive cell compatibility testing of bone marrow derived cells with the ND Infusion Catheter revealed that the catheter preserved cell viability and functionality, Stefanie Dimmeler, PhD and Director of the Institute of Cardiovascular Regeneration, Centre of Molecular Medicine stated. The testing proved that the cells are compatible with the ND Infusion Catheter. We see this as potential improvements in safety and clinical outcomes related to cell function and efficacy in patients, Dr. Dimmeler offered.

Safety was top-of-mind when we initiated the first-in-man procedure in Frankfurt. We are elated to report that the procedures outcomes were successful, Dr. Dib stated. Earlier studies revealed that the ND Infusion Catheter reduces cellular clumping, preserves cell viability, improves dispersion and reduces radial forces on the vessel walls during balloon inflation; which collectively might improve patient safety and clinical outcomes.

TRI Medicals Ron Anson, Vice President of Business Development shared The catheters unique design features provide physicians with a valuable new tool in the delivery of specified fluids such as stem cells. We expect to see significant growth in the stem cell research marketplace for the new, state-of-the-art ND Infusion Catheter.

ABOUT TRI Medical TRI Medical is a privately held, medical device development company. TRI Medical is dedicated to providing a pathway to regulatory approval that is efficient, predictable and cost effective.

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Media inquiries regarding TRI Medical, its capabilities and for additional information regarding the ND Infusion Catheter contact: DeAnn Dana Phone: 480.309.2884 Email: DDana(at)TRImedical.com TRI Medical website: http://www.trimedical.com

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First-in-man procedure utilizes a new method of stem cell delivery

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Study Links Sex Hormone Levels in the Blood to Risk of Sudden Cardiac Arrest Measuring the levels of sex hormones in patients blood may identify patients likely to suffer a sudden cardiac arrest, a heart rhythm disorder that is fatal in 95 percent of patients. A new study, published online by the peer-reviewed journal Heart Rhythm, shows that lower levels of testosterone, the predominant male sex hormone, were found in men who had a sudden cardiac arrest. Higher levels of estradiol, the major female sex hormone, were strongly associated with greater chances of having a sudden cardiac arrest in both men and women. CONTACT: Sally Stewart, 310-248-6566; Email sally.stewart@cshs.org

Cedars-Sinai Shortens Premature Infants Intensive Care Stays by 21 Percent in Past Three Years The amount of time premature babies spend in Cedars-Sinais Neonatal Intensive Care Unit, part of the Maxine Dunitz Childrens Health Center, has declined dramatically during the past three years, with the average length of stay dropping from 21 days to 17 days. In recent years there have been some notable medical advances, such as personalized nutrition therapy that helps the smallest infants gain weight, nonsurgical procedures to heal heart defects and new medical protocols for mothers likely to deliver a premature infant. All have contributed to more rapidly improving the health of premature infants and shortening the infants hospital stays. But one of the main reasons for the shorter hospitalizations is a renewed emphasis on coordinating each babys various and complex health needs. CONTACT: Soshea Leibler, 213-215-8000; Email soshea.leibler@cshs.org

Combining Antibodies, Iron Nanoparticles and Magnets Steers Stem Cells to Injured Organs Researchers at the Cedars-Sinai Heart Institute infused antibody-studded iron nanoparticles into the bloodstream to treat heart attack damage. The combined nanoparticle enabled precise localization of the bodys own stem cells to the injured heart muscle. The study, which focused on laboratory rats, was published in the online peer reviewed journal Nature Communications. The study addresses a central challenge in stem cell therapeutics: how to achieve targeted interactions between stem cells and injured cells. CONTACT: Sally Stewart, 310-248-6566; Email sally.stewart@cshs.org

Cedars-Sinai Presents Educational Program on Pituitary Disorders for Patients and Families Disorders of the pituitary gland often cause gradual onset of challenging and difficult-to-manage symptoms, and it is not uncommon for patients to consult doctor after doctor in search of an accurate diagnosis and the hope of treatment. In a one-day conference in Huntington Beach on Sept. 28, pituitary experts from Cedars-Sinai will provide an update for patients and their families on the most recent advances in the diagnosis and treatment of pituitary disorders. Patients will be able to engage in discussions and Q&A sessions with the faculty. CONTACT: Sandy Van, 808-526-1708; Email sandy@prpacific.com

Researchers Developing Noninvasive Method for Diagnosing Common, Painful Back Condition An interdisciplinary research team in the Cedars-Sinai Biomedical Imaging Research Institute, Department of Biomedical Sciences, Regenerative Medicine Institute and Department of Surgery received a grant from the National Institutes of Health (NIH) to develop the first imaging technique used to identify biomarkers that could indicate patients have a painful, degenerative back condition. Biomarkers are certain body substances, such as proteins or body fluids that can indicate specific health conditions. When noninvasive imaging procedures can identify exactly where the biomarkers are, researchers may alleviate the need for painful and invasive diagnostic procedures and, in the future, provide targeted, stem cell-based therapies to patients with the condition. CONTACT: Cara Martinez, 310-423-7798; Email cara.martinez@cshs.org

Cedars-Sinais New Comprehensive Transplant Center Opens The new home of the Cedars-Sinai Comprehensive Transplant Center opens Monday and consolidates the clinical and administrative services for liver, kidney, lung and pancreas transplant patients. The four programs were previously housed at several locations on the 24-acre medical center campus, but now transplant patients can have nearly all of their medical needs addressed at one location. The three-story facility covers 36,500 square feet and is located at 8900 Beverly Blvd., two blocks from the main medical center campus. The new center has 22 exam rooms, infusion therapy and phlebotomy services, patient education space and an outpatient procedure room. Two floors of underground parking and valet parking service are available to patients and their families. (High resolution photos available upon request) CONTACT: Laura Coverson, 310-423-5215; Email laura.coverson@cshs.org

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Cedars-Sinai Medical Tip Sheet for Sept. 2014

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10-Sep-2014

Contact: Sally Stewart sally.stewart@cshs.org 310-248-6566 Cedars-Sinai Medical Center

LOS ANGELES Researchers at the Cedars-Sinai Heart Institute infused antibody-studded iron nanoparticles into the bloodstream to treat heart attack damage. The combined nanoparticle enabled precise localization of the body's own stem cells to the injured heart muscle.

The study, which focused on laboratory rats, was published today in the online peer reviewed journal Nature Communications. The study addresses a central challenge in stem cell therapeutics: how to achieve targeted interactions between stem cells and injured cells.

Although stem cells can be a potent weapon in the fight against certain diseases, simply infusing a patient with stem cells is no guarantee the stem cells will be able to travel to the injured area and work collaboratively with the cells already there.

"Infusing stem cells into arteries in order to regenerate injured heart muscle can be inefficient," said Eduardo Marbn, MD, PhD, director of the Cedars-Sinai Heart Institute, who led the research team. "Because the heart is continuously pumping, the stem cells can be pushed out of the heart chamber before they even get a chance to begin to heal the injury."

In an attempt to target healing stem cells to the site of the injury, researchers coated iron nanoparticles with two kinds of antibodies, proteins that recognize and bind specifically to stem cells and to injured cells in the body. After the nanoparticles were infused into the bloodstream, they successfully tracked to the injured area and initiated healing.

"The result is a kind of molecular matchmaking," Marbn said. "Through magnetic resonance imaging, we were able to see the iron-tagged cells traveling to the site of injury where the healing could begin. Furthermore, targeting was enhanced even further by placing a magnet above the injured heart."

The Cedars-Sinai Heart Institute has been at the forefront of developing investigational stem cell treatments for heart attack patients. In 2009, Marbn and his team completed the world's first procedure in which a patient's own heart tissue was used to grow specialized heart stem cells. The specialized cells were then injected back into the patient's heart in an effort to repair and regrow healthy muscle in a heart that had been injured by a heart attack. Results, published in The Lancet in 2012, showed that one year after receiving the stem cell treatment, heart attack patients demonstrated a significant reduction in the size of the scar left on the heart muscle.

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Combining antibodies, iron nanoparticles and magnets steers stem cells to injured organs

Kotlikoff lab

Optogenetic proteins enable visualization of a developing heart.

New technologies involving optogenetic proteins, which use light to control and observe cells with unprecedented precision, have begun to illuminate processes underlying cellular behavior and the effects of cell- and gene-based therapies. Cornell researchers are developing advanced forms of these proteins to create a toolkit to make them more widely available to scientists.

With a five-year, $3.1 million grant from the National Institutes of Healths Heart, Lung and Blood Institute, the team will develop the Cornell Heart, Lung and Blood Resource for Optogenetic Mice (CHROMus), which will incorporate optogenetic proteins in mice and human stem cells. Scientists use such tools to control and observe how different types of cells function and interact.

We will target these tools so that they can be combined to study diseases of the heart, lungs, vasculature and blood, said Dr. Michael Kotlikoff, the Austin O. Hooey Dean of Veterinary Medicine at Cornells College of Veterinary Medicine and the projects lead investigator. Researchers will be able to use them to address a broad set of health issues, including heart attack, stroke, asthma and immune diseases.

Marrying optics and genetics, optogenetics enables scientists to use light to trigger and monitor the behavior of cells engineered to contain one or both of two types of designer proteins: effectors, which respond to light by activating the cell they are on, or sensors, which fluoresce when a cell has been activated.

Effectors and sensors can be engineered into specific kinds of cells and color-coded, letting scientists noninvasively trigger one type to see how another type responds. One can see different cell types light up in living animals, giving direct insight into specific cells roles in complex biological systems.

The lines of CHROMus mice developed in this project are designed to be easily crossbred, creating a combinatorial platform that will allow scientists to customize sets of effectors and sensors including new sensors from the Kotlikoff lab into the specific cell types they want to study.

For example, our lab is particularly interested in using these tools to study the control of blood flow to tissues what happens before, during and after major events like stroke and cardiac infarction, and how abnormal rhythms develop after heart injury, said Kotlikoff. Arrhythmias following a heart attack are the single most common cause of acute death in the western world, and how they can be prevented requires a better understanding of how, why and where they arise. Optogenetic tools let us look directly at relevant cells throughout the heart to determine their role in these dangerous and often fatal events.

The tools will be designed to allow scientists to ask and answer similar questions related to vascular and lung diseases, such as the role of the immune system in asthma and stroke, and how therapeutic stem cells integrate within the tissue that they are designed to repair.

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Optogenetics shed light on cardiac, lung, immune disease