ScienceDaily (June 7, 2012) Scientists at the Gladstone Institutes have for the first time transformed skin cells -- with a single genetic factor -- into cells that develop on their own into an interconnected, functional network of brain cells. The research offers new hope in the fight against many neurological conditions because scientists expect that such a transformation -- or reprogramming -- of cells may lead to better models for testing drugs for devastating neurodegenerative conditions such as Alzheimer's disease.

This research comes at a time of renewed focus on Alzheimer's disease, which currently afflicts 5.4 million people in the United States alone -- a figure expected to nearly triple by 2050. Yet there are no approved medications to prevent or reverse the progression of this debilitating disease.

In findings appearing online June 7 in Cell Stem Cell, researchers in the laboratory of Gladstone Investigator Yadong Huang, MD, PhD, describe how they transferred a single gene called Sox2 into both mouse and human skin cells. Within days the skin cells transformed into early-stage brain stem cells, also called induced neural stem cells (iNSCs). These iNSCs began to self-renew, soon maturing into neurons capable of transmitting electrical signals. Within a month, the neurons had developed into neural networks.

"Many drug candidates -- especially those developed for neurodegenerative diseases -- fail in clinical trials because current models don't accurately predict the drug's effects on the human brain," said Dr. Huang, who is also an associate professor of neurology at the University of California, San Francisco (UCSF), with which Gladstone is affiliated. "Human neurons -- derived from reengineered skin cells -- could help assess the efficacy and safety of these drugs, thereby reducing risks and resources associated with human trials."

Dr. Huang's findings build on the work of other Gladstone scientists, starting with Gladstone Investigator, Shinya Yamanaka, MD, PhD. In 2007, Dr. Yamanaka used four genetic factors to turn adult human skin cells into cells that act like embryonic stem cells -- called induced pluripotent stem cells.

Also known as iPS cells, these cells can become virtually any cell type in the human body -- just like embryonic stem cells. Then last year, Gladstone Senior Investigator Sheng Ding, PhD, announced that he had used a combination of small molecules and genetic factors to transform skin cells directly into neural stem cells. Today, Dr. Huang takes a new tack by using one genetic factor -- Sox2 -- to directly reprogram one cell type into another without reverting to the pluripotent state.

Avoiding the pluripotent state as Drs. Ding and Huang have done is one approach to avoiding the potential danger that "rogue" iPS cells might develop into a tumor if used to replace or repair damaged organs or tissue.

"We wanted to see whether these newly generated neurons could result in tumor growth after transplanting them into mouse brains," said Karen Ring, UCSF Biomedical Sciences graduate student and the paper's lead author. "Instead we saw the reprogrammed cells integrate into the mouse's brain -- and not a single tumor developed."

This research, which was performed at the Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, has also revealed the precise role of Sox2 as a master regulator that controls the identity of neural stem cells. In the future, Dr. Huang and his team hope to identify similar regulators that guide the development of specific neural progenitors and subtypes of neurons in the brain.

"If we can pinpoint which genes control the development of each neuron type, we can generate them in the petri dish from a single sample of human skin cells," said Dr. Huang. "We could then test drugs that affect different neuron types -- such as those involved in Parkinson's disease -- helping us to put drug development for neurodegenerative diseases on the fast track."

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Skin cells reprogrammed into brain cells

A team of scientists has discovered what could be a novel source for researching and potentially treating Alzheimer's disease and other conditions involving the destruction of brain cells.

Researchers at the University of California San Francisco-affiliated Gladstone Institutes converted skin cells from mice and humans into brain stem cells with the use of a protein called Sox2. Using only this protein to transform the skin cells into neuron stem cells is unusual. Normally, the conversion process is much more complex.

Neuron stem cells are cells that can be changed into the nerve cells and the cells that support them in the brain. The neuronal stem cells formed in this study are unique because they were prepared in a way the prevented them from becoming tumors, which is what often happens as stem cells differentiate, explained David Teplow, professor of neurology and director of the Easton Center for Alzheimer's Disease Research at UCLA. Teplow was not involved in the study, but is familiar with this type of research.

These immature brain stem cells then developed into different types of functional brain cells, which were eventually able to be integrated into mouse brains.

Jonathan Selig/Getty Images

The idea that these cells can become fully functioning brain tissue is significant, the authors explained, because by becoming part of the brain, the cells can replace the cells killed off by the disease process.

These cells also offer a potential way to learn about the mechanisms behind neurodegenerative disorders as well as lead to research into new drugs, explained Dr. Yadong Huang, a study co-author and associate investigator at the Gladstone Institute of Neurological Disease.

"The next step is, we are trying to get these skin cells from patients with this disease so we can reprogram and convert the diseased cells into these neuron stem cells and develop those into neurons in culture," he said.

After that, researchers can study how these diseases develop based on what's observed in culture dishes.

"It's really hard to get neurons from human brains for research, and now, we can generate them," Huang said. "Secondly, we can do some drug screening. If we have patient-specific neurons in culture, we can test some or develop some drugs to see how they work on these neurons."

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Skin Cells Turned Into Brain Cells

It's always troubling to see a misunderstanding concerning a recent scientific discovery. The latest concerns an Israeli team of scientists, led by Lior Gepstein, that converted skin cells from two patients with heart attack into stem cells and then heart cells.

SourceFed, one of my favorite channels on YouTube, proclaimed that Gepstein's study means that a cure for heart disease is "10, 15 years out." Similar statements were also circulated by The Guardian, The Los Angeles Times, CBS News, and others.

However, the claims that SourceFed and other news outlets have made are not true. If anything, the field of heart regeneration is moving away from what the study did. If there is a cure for heart attack in 10 to 15 years, it will not be because of this study.

Generating stem cells from skin cells is relatively old news. This feat was first performed in 2006 for mice (2007 for humans) concurrently by two teams of scientists led by Shinya Yamanaka in Japan and James Thomson in the United States, respectively. Since then, the technology has evolved so fast that generating heart cells from stem cells is truly nothing new.

Stem cells often differentiate into heart cells, or cardiomyocytes, without much technical intervention. Even I, a mere undergraduate student, have generated beating heart cells several times without much trouble, from mice and rat skin cells. And I'm not even in the field of heart regeneration. I work with stem cells in neurobiology.

The technique to generate heart cells from skin-derived stem cells (or induced pluripotent stem cells) has existed for a long time. After a brief search on Google Scholar, I found a paper published in 2008 detailing how to generate heart cells from skin cells. This may not seem like a long time ago, but in the stem-cell world, that's almost an eon.

So if we have been able to generate heart cells for such a long time, why has no one actually successfully transplanted heart cells into patients? One of the reasons is that there are so many different problems with not only transplanting heart cells onto a beating heart but also with the induced pluripotent stem cells that are derived from skin cells.

When a heart is damaged, scar tissues grow over the damaged part of the heart. The scar tissue does not function like regular heart cells. Instead of beating, the scar tissue just sits there, not doing anything and getting in the way of the beating heart. It's just like a scab on your arm from a scrape. The only difference is that the scab eventually comes off, because your skin is constantly making new cells, but the scar on your heart doesn't, because heart cells rarely regenerate, if at all.

Transplanting new heart cells without removing the scars is like putting a new layer of skin over the old scab and expecting the scab to go away. The old scab doesn't go away. More likely, the transplanted tissue will just die off.

As a result, instead of trying to transplant new tissue, the field of heart regeneration is now trying to transform the cells in scar tissue into beating heart cells. Though there are also problems with this new direction, it opens up ways of solving a whole host of other problems that plague heart-cell transplantation.

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Rui Dai: Our Misunderstanding of Stem Cells

ALPHARETTA, Ga.--(BUSINESS WIRE)--

SANUWAVE Health, Inc. (SNWV), today announced the publication of peer-reviewed, preclinical research that demonstrates the ability of the Companys Extracorporeal Shock Wave Technology (ESWT) to stimulate proliferation of periosteal adult stem cells (cambium cells) within the body and subsequently form bone. In addition, the combination of ESWT-proliferated adult stem cells and a bioactive scaffold regenerated more bone than a bioactive scaffold alone.

The publication, titled The Use of Extracorporeal Shock Wave-Stimulated Periosteal Cells for Orthotopic Bone Regeneration, appeared in the online edition of Tissue Engineering, Part A as an ePublication ahead of print. The abstract of the publication can be viewed online at: http://online.liebertpub.com/doi/abs/10.1089/ten.TEA.2011.0573.

Led by Myron Spector, M.D., a professor and researcher at Harvard-MIT Division of Health Sciences and Technology, the authors stated, This study investigated a novel approach for treatment of bone loss, which has potential for many clinical situations where bone apposition is required (e.g., vertical ridge augmentation, regrowing bone following tumor resection, and regenerating bone lost at sites of osteolysis or bone degeneration).

The cambium cells of the periosteum (outer membrane covering bone) currently have limited suitability for clinical applications in their native state due to their low cell number (only 2 to 5 cells thick). However, ESWT has been shown to cause a rapid increase in periosteal cambium cell numbers and subsequent periosteal osteogenesis (bone formation). The advantages of adding a scaffold as we did in this study are threefold: the scaffold contours the new bone, it helps maintain bone at the implant site, and it creates a space to allow the periosteal cells to further proliferate and fill the scaffold.

The authors concluded, The ESWT-stimulated samples of tibial bone outperformed the control group in all key outcome variables, and the study results therefore demonstrated the efficacy of ESWT-stimulated periosteum for bone generation. These results successfully demonstrated the efficacy of periosteum stimulated by ESWT technology for bone generation.

In the first phase of this research, the authors successfully demonstrated that ESWT increased the thickness of the cambium layer surrounding bone and the number of cambium cells within that layer. This proliferation of adult stem cells is an important part of many tissue engineering strategies. Then, in a novel second phase, the authors combined the ESWT-proliferated adult stem cells with a porous calcium phosphate scaffold that is commonly utilized in clinical applications to stimulate bone regeneration. A comparator control group received the scaffold alone with no prior ESWT treatment. The results were statistically significant and favored the ESWT group. In fact, at two weeks post-surgery, there was a significant increase in all key outcome variables for bone growth favoring the group that received ESWT prior to being combined with a scaffold compared with the group that received only the scaffold.

Summary of Key Study Findings

About SANUWAVE Health, Inc. SANUWAVE Health, Inc. (www.sanuwave.com) is an emerging regenerative medicine company focused on the development and commercialization of noninvasive, biological response activating devices for the repair and regeneration of tissue, musculoskeletal and vascular structures. SANUWAVEs portfolio of products and product candidates activate biologic signaling and angiogenic responses, including new vascularization and microcirculatory improvement, helping to restore the bodys normal healing processes and regeneration. SANUWAVE intends to apply its PACE technology in wound healing, orthopedic/spine, plastic/cosmetic and cardiac conditions. Its lead product candidate for the global wound care market, dermaPACE, is CE marked and has Canadian device license approval for the treatment of the skin and subcutaneous soft tissue. In the U.S., dermaPACE is currently under the FDAs Premarket Approval (PMA) review process for the treatment of diabetic foot ulcers. SANUWAVE researches, designs, manufactures, markets and services its products worldwide, and believes it has demonstrated that its technology is safe and effective in stimulating healing in chronic conditions of the foot (plantar fasciitis) and the elbow (lateral epicondylitis) through its U.S. Class III PMA approved Ossatron device, as well as stimulating bone and chronic tendonitis regeneration in the musculoskeletal environment through the utilization of its Ossatron, Evotron and orthoPACE devices in Europe.

Forward-Looking Statements This press release may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, such as statements relating to financial results and plans for future business development activities, and are thus prospective. Forward-looking statements include all statements that are not statements of historical fact regarding intent, belief or current expectations of the Company, its directors or its officers. Investors are cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, many of which are beyond the Companys ability to control. Actual results may differ materially from those projected in the forward-looking statements. Among the key risks, assumptions and factors that may affect operating results, performance and financial condition are risks associated with the marketing of the Companys product candidates and products, unproven pre-clinical and clinical development activities, regulatory oversight, the Companys ability to manage its capital resource issues, competition, and the other factors discussed in detail in the Companys periodic filings with the Securities and Exchange Commission. The Company undertakes no obligation to update any forward-looking statement.

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SANUWAVE Technology Shown to Proliferate Stem Cells and Form Bone

GRAND RAPIDS, MI -- A stem cell treatment investigated for Huntingtons disease holds out hope that scientists will someday be able to reverse damage caused by the degenerative brain disorder.

The technique, which uses reprogrammed skin cells from a Huntingtons patient, successfully restored motor functions in rats, said Dr. Patrik Brundin, a Van Andel Institute researcher who was involved in the study.

Its an interesting step, one weve been hoping for, he said. Its exciting.

The technique also will be tested in treatments for Parkinsons disease, said Brundin, who came to VAI from Sweden in October to lead the institutes Parkinsons research.

Scientists from Sweden, South Korea and the U.S. collaborated on the study, which was published online Monday in the journal Stem Cells.

Brundin said researchers took stem cells derived from the skin of a patient with Huntingtons disease and converted them to brain cells or nerve cells in culture dishes in the lab. The cells were transplanted into the brains of rats that had an experimental form of Huntingtons, and the rats motor functions improved.

The unique features of the (stem cell approach) means that the transplanted cells will be genetically identical to the patient, Jihwan Song, an associate professor at CHA University in Seoul and co-author of the study, said in a statement released by VAI. Therefore, no medications that dampen the immune system to prevent graft rejection will be needed.

Brundin estimated the research might lead to treatments for humans in five to 10 years, although he acknowledged a timeframe is difficult to predict. Researchers are eager to find a new treatment for Huntingtons because there is nothing really powerful to offer currently, he said.

Huntingtons is a genetic disorder affecting one in every 10,000 Americans that slowly diminishes a persons ability to walk, talk and reason. A child of a parent who has Huntingtons has a 50 percent chance of inheriting the gene that causes it.

Medications can relieve some symptoms in some cases, but there are no treatments available that can slow the disease, according to the Huntingtons Disease Society of America.

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First treatment for Huntington's disease shows promise in rats, Van Andel Institute scientist says

KIAH

12:01 p.m. CDT, May 30, 2012

How do you mend a broken heart? Thanks to scientists in Israel, we might soon have an answer.

Dr. Lior Gepstein and his team at Technion-Israel Institute of Technology managed to take skin cells from ailing heart patients and by adding three genes and valproic acid (used to treat epilepsy), they turned the cells into beating heart tissue.

And it was not just any old heart cells, but, according to Gepstein, "heart cells that are healthy, that are young and resemble heart cells at the day that the patient was born."

The researchers put the new beating heart tissue into rat hearts and saw it was not rejected, but seemed to establish connections with the rodents' tissue.

Stem cell experts praised the research as promising but urged people not to expect to be stopping by the clinic for a fresh heart any time soon. Gepstein's researchers say clinical trials should begin within the next 10 years.

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Skin cells turned into beating heart cells

Scientists turn skin cells into healthy heart tissue

Kate Kelland (Reuters) / 26 May 2012

The researchers said there were still many years of testing and refining ahead. But the results meant they might eventually be able to reprogramme patients cells to repair their own damaged hearts.

We have shown that its possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young - the equivalent to the stage of his heart cells when he was just born, said Lior Gepstein, who led the work.

The researchers, whose study was published in the European Heart Journal on Wednesday, said clinical trials of the technique could begin within 10 years.

Heart failure is a debilitating condition in which the heart is unable to pump enough blood around the body. It has become more prevalent in recent decades as advances in medical science mean many more people survive heart attacks. At the moment, people with severe heart failure have to rely on mechanical devices or hope for a transplant.

Researchers have been studying stem cells from various sources for more than a decade, hoping to capitalise on their ability to transform into a wide variety of other kinds of cell to treat a range of health conditions.

There are two main forms of stem cells - embryonic stem cells, which are harvested from embryos, and reprogrammed human induced pluripotent stem cells (hiPSCs), often originally from skin or blood.

Gepsteins team took skin cells from two men with heart failure aged 51 and 61 and transformed them by adding three genes and then a small molecule called valproic acid to the cell nucleus.

They found that the resulting hiPSCs were able to differentiate to become heart muscle cells, or cardiomyocytes, just as effectively as hiPSCs that had been developed from healthy, young volunteers who acted as controls for the study.

Originally posted here:
Scientists turn skin cells into healthy heart tissue

Editor's Choice Main Category: Cardiovascular / Cardiology Article Date: 25 May 2012 - 0:00 PDT

Current ratings for: 'Skin Cells From Heart Failure Patients Made Into Healthy New Heart Muscle Cells'

4 (1 votes)

This achievement is significant, as it opens up the prospect of treating heart failure patients with their own, human-induced pluripotent stem cells (hiPSCs) to fix their damaged hearts.

Furthermore, the cells would avoid being rejected as foreign as they would be derived from the patients themselves. The study is published in the European Heart Journal. However, the researchers state that it could take a minimum of 5 to 10 years before clinical trials could start due to the many obstacles that must be overcome before using hiPSCs in humans is possible.

Although there has been advances in stem cell biology and tissue engineering, one of the major problems scientists have faced has been lack of good sources of human heart muscle cells and rejection by the immune system. Furthermore, until now, scientific have been unable to demonstrate that heart cells created from hiPSCs could integrate with existing cardiovascular tissue.

"What is new and exciting about our research is that we have shown that it's possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are health and young - the equivalent to the stage of his heart cells when he was just born," said Professor Lior Gepstein, Professor of Medicine (Cardiology) and Physiology at the Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Technion-Israel Institute of Technology and Rambam Medical Center in Haifa, Israel, who led the study.

In the study, Professor Gepstein, Ms Limor Zwi-Dantsis, and their colleagues retrieved skin cells from two male heart failure patients, aged 51 and 61 years, and reprogrammed the cells by delivering 3 transcription factors (Sox2, Oct4, and Klf4) in addition to a small molecule called valproic acid, to the cell nucleus. The team did not include a transcription factor called c-Myc as it is a known cancer-causing gene.

Professor Gepstein said:

In addition, the team used an alternative strategy involving a virus transferred reprogramming data to the cell nucleus. However, the team removed the virus after the information had been transferred in order to avoid insertional oncogenesis.

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Skin Cells From Heart Failure Patients Made Into Healthy New Heart Muscle Cells

Scientists on Wednesday reported that they have for the first time taken skin cells from heart attacks patients and turned them into healthy heart tissue that could hopefully be used to one day repair damaged heart muscle.

The healthy, beating heart tissue was grown successfully in the lab from human-induced pluripotent stem cells (hiPSCs), and while scientists said they were not safe enough to put back into human patients, they appeared to work well with other cells when implanted into rats. HiPSCs are a recently discovered source far less controversial than use of embryonic stem cells. And, because the transplanted hiPSCs come from the individual, it could resolve the problems seen with tissue and organ rejection.

While the technique has shown promise in rats, the scientists say there are numerous obstacles to overcome and it could take up to ten years or longer before clinical trials could be available for humans. Even so, it is a significant advance in the quest for replacement cell therapy for heart failure patients.

More people are surviving following a heart attack than ever before and therefore the number of people living with a damaged heart and heart failure is increasing, Nicholas Mills, a consultant cardiologist at Edinburgh University, told The Guardian. Unfortunately, the body has only very limited capacity to repair the heart following a heart attack. There is therefore an urgent need to develop effective and safe treatments to regenerate the heart.

Recent research has shown that hiPSCs could be derived from young and healthy people and are capable of transforming into heart cells. However, researchers have not been able to obtain those cells from elderly and diseased patients. And until now, researchers have not been able to show that heart cells created from hiPSCs could integrate with existing heart tissue.

What is new and exciting about our research is that we have shown that its possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young the equivalent to the stage of his heart cells when he was just born, said lead researcher Professor Lior Gepstein, of Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Technion-Israel Institute of Technology and Rambam Medical Center in Haifa, Israel.

For their study, published in the European Heart Journal, Limor Zwi-Dantsis, a PhD student in the Sohnis Research Laboratory, Gepstein and colleagues took skin cells from two male heart failure patients (ages 51 and 61) and reprogrammed them with three genes (Sox2, Klf4 and Oct4), followed by a small molecule (valproic acid) to the cell nucleus.

The team also used an alternative strategy that involved a virus that delivered reprogramming information to the cell nucleus but which was capable of being removed afterward to avoid insertional oncogenesis.

Using these methods, the hiPSCs were able to differentiate to become cardiomyocytes (heart muscle cells) just as effectively as hiPSCs that had been developed from healthy, young volunteers. The researchers were then able to make cardiomyocytes develop into heart muscle tissue, which they cultured together with pre-existing cardiac tissue. The tissues were beating together within 48 hours, said the researchers.

The researchers transplanted the new tissue into the hearts of healthy rats and found that the grafted tissue started to establish connections with the cells in the host tissue.

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Human Skin Cells Turned Into Healthy Heart Muscle

Dr. John D. Cunningham / Getty Images

In a medical first, scientists in Haifa, Israel, took skin cells from two heart failure patients and reprogrammed them into stem cells that generated healthy, beating heart muscle cells in the lab. Though human testing is likely a decade off, the hope is that such cells can be used to help people with heart failure repair their damaged hearts with their own skin cells.

In the current study, scientists first mixed the newly developed heart cells with pre-existing heart tissue within days, the cells were beating together. The heart tissue was then transplanted into rats, where it integrated with the rats healthy heart cells.

What is new and exciting about our research is that we have shown that its possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young the equivalent to the stage of his heart cells when he was just born, says lead researcherDr. Lior Gepstein, a senior clinical electrophysiologist at Rambam Medical Center in Israel, said in a statement.

The researchers were pleased to find that the cells made from the two heart failure patients, ages 51 and 61, generated heart muscle cells that were just as effective as those developed from healthy, young controls.

(MORE: Study During Beijing Olympics Shows How Pollution Harms the Heart)

If the technology works in human hearts, it could potentially prevent problems of immune rejection, since the cells would be the patients own. It would also avoid the moral issues surrounding the use of embryonic stem cells, since such reprogrammed stem cells or human induced pluripotent stem (iPS) cells do not use embryos.

But its still too early to predict whether the procedure could be successful humans. The new study involved cells from only two patients and were transplanted only into healthy animals. The authors note that human clinical trials are likely at least five or 10 years away. Further, creating iPS cells is not an easy or efficient process; its not clear whether enough cells could be made quickly enough to repair the broad-scale damage that occurs after a heart attack.

Reprogramming skin cells to become stem cells also introduces the potential for the cells to grow out of control and become cancerous. The Israeli researchers took additional steps removing certain transcription factors and viral factors to reduce the risk of cancer. But these hurdles would have to be revisited if the technique is tested in human patients.

This is an interesting paper, but very early and its really important for patients that the promise of such a technique is not oversold, John Martin, a professor of cardiovascular medicine at University College London, told Reuters.The chances of translation are slim and if it does work it would take around 15 years to come to clinic.

Continued here:
Scientists Turn Skin Cells into Healthy Heart Cells

In the first procedure of its kind, skin cells taken from patients suffering from heart failure were reprogrammed and changed into heart muscle cells. Not only were the transformed cells healthy, but they were also transplanted into the hearts of rats and were able to integrate with the existing heart tissue.

Published in the European Heart Journal, the research examined the use of human-induced pluripotent stem cells (hiPSCs) to treat damaged hearts. HiPSCs are cells that are derived from other cells in a persons body.

We were able to show [in earlier studies] that you can take these hiPSCS from healthy heart patients and coax them into bonafide heart cells, lead author Lior Gepstein, professor of medicine (cardiology) and physiology at the Technion-Israel Institute of Technology and Rambam Medical Center in Haifa, Israel, told FoxNews.com. The question we asked in this study was whether you can do the same from an elderly individual that had suffered from advance heart failure.

Because hiPSCs are derived from the person in need of the stem cells, they could potentially help to bypass the painful process of rejection that many transplant patients go through. According to Gepstein, if this process is perfected, it could lead to much more localized treatments.

When there is significant damage from a heart attack, or with heart failure, where the heart doesnt pump enough blood into circulation, patients usually need a heart transplant, Gepstein said. But perhaps in the future, we can take a small sample of skin and convert them into stem cells specific to that patient. Then we can only replace the area with scar tissue rather than replace the dying heart.

In order to transform the skin cells into hiPSCs, Gepstein and his colleagues gave them a reprogramming cocktail, which involved delivering three genes (Sox2, Klf4 and Oct4), followed by a small molecule called valproic acid, to the nucleus of the cell.

This process turned the skin cells into heart muscle cells, or cardiomyocytes, which the researchers were able to subsequently turn into heart muscle tissue by culturing them together with cardiac tissue.

We converted the cells back into a state that resembles their early state in the embryo, Gepstein said. So they highly resemble the patients cells at the time they were born. When you give them proper conditions, they can become any type of cell in the body.

This area of study has advanced very rapidly, Gepstein added. You can take almost any type of adult cells - hair follicles, blood cells, etc. - and reprogram them to make hiPSCS cells. Skin cells are the easiest way to do it, and you dont need a lot of them.

Once the tissue had formed, it was transplanted into the hearts of healthy rats, where it successfully grafted and integrated with the existing tissue.

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Scientists convert skin cells into full functioning heart cells

WEDNESDAY, May 23 (HealthDay News) -- In a medical science first, researchers turned skin cells from heart failure patients into heart muscle cells that may then be used to fix damaged cardiac tissue.

The researchers said the achievement -- done initially with rats -- opens up the prospect of using heart failure patients' own stem cells -- a form of cell called human-induced pluripotent stem cells (hiPSCs) -- to repair damaged hearts. And since the reprogrammed stem cells would originate with the patient, their immune systems would not reject the cells as foreign, the researchers explained.

They added, however, that many obstacles must be overcome before it would be possible to use hiPSCs in humans this way, and any clinical trial would be at least five to 10 years away.

"We have shown that it's possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young -- the equivalent to the stage of his heart cells when he was just born," study leader Lior Gepstein said in a European Heart Journal news release. The study's findings are scheduled for online publication in the journal May 23.

Gepstein is professor of medicine (cardiology) and physiology at the Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine at the Technion Israel Institute of Technology and Rambam Medical Center in Haifa, Israel.

One expert in the United States applauded the achievement.

"The ability to source a patient's own skin cells and transform them into heart muscle is truly revolutionary," said Dr. Gregory Fontana, chairman of cardiothoracic surgery at Lenox Hill Hospital in New York City.

The results are "another step toward the treatment of heart failure with stem cells," he said. "Although further work is needed, this work represents another step closer to the clinic."

In the study, the researchers retrieved skin cells from two male heart failure patients, ages 51 and 61, and then reprogrammed them in the lab to develop into heart muscle tissue, which was then blended with pre-existing heart tissue. Within 24 to 48 hours, the tissues were beating together.

The new tissue was transplanted into healthy rat hearts and started to establish connections with the cells of the rat hearts. Success in animal experiments does not necessarily translate to success in humans, however.

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Scientists Turn Skin Cells Into Cardiac Cells to Help Failing Hearts

People who suffer from heart failure could someday be able to use their own skin stem cells to regenerate their damaged heart tissue, according to a new Israeli study.

Researchers took stem cells from the skin of two patients with heart failure and genetically programmed them to become new heart muscle cells. They then transplanted the new cells into healthy rats and found that the cells integrated with cardiac tissue that already existed.

The study, published in European Heart Journal, marks the first time ever that scientists could use skin cells from people with heart failure and transform damaged heart tissue this way.

The newly generated cells turned out to be similar to embryonic stem cells, which can potentially be programmed to grow into any type of cell.

"What is new and exciting about our research is that we have shown that it's possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young the equivalent to the stage of his heart cells when he was just born," Dr. Lior Gepstein, lead researcher and a senior clinical electrophysiologist at Rambam Medical Center in Haifa, Israel, said in a news release.

The findings open up the possibility, the authors wrote, that people can use their own skin cells to repair their damaged hearts, which could prevent the problems associated with using embryonic stem cells.

"This approach has a number of attractive features," said Dr. Tom Povsic, an interventional cardiologist at Duke University Medical Center. "We can get the cells that you start with from the patient himself or herself. It avoids the ethical dilemma associated with embryonic stem cells and it removes the possibility of rejection of foreign stem cells by the immune system." Povsic was not involved with the Israeli study.

Another advantage of using skin cells is that other types of cells taken from patients themselves, such as bone marrow cells, could potentially lead to the development of unhealthy tissue.

"If a patient is already sick with heart disease, one of the reasons it may develop is that stem cells weren't able to repair the heart the way they should," Povsic added. Skin cells, he explained, are generally healthy.

"It is very exciting and very interesting, but we are far away from taking this to patients," said Dr. Marrick Kukin, director of the Heart Failure Program at St. Luke's-Roosevelt Hospital who was also not involved in the Israeli study.

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Can Stem Cells Repair Heart Tissue?

(CBS News) A new study of patients with heart failure found a novel treatment approach might reverse the damage that has long been considered irreversible: Fixing their damaged hearts using stem cells derived by their own skin cells.

Stem cells heal heart attack scars, regrow healthy muscle Stem cells cure heart failure? What "breakthrough" study shows

In what scientists are calling a first, skin cells were taken from heart failure patients and transformed into stem cells, which were then turned into heart muscle cells capable of beating - albeit in a petri dish.

The treatment approach has scientists buzzing because it avoids the risk of possible immune system rejection from transplanting "foreign" stem cells, since the cells came from patients' own bodies.

"What is new and exciting about our research is that we have shown that it's possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young - the equivalent to the stage of his heart cells when he was just born," the study's author Professor Lior Gepstein, professor of cardiology and physiology at the Technion-Israel Institute of Technology in Haifa, said in a news release.

Just how do skin cells become heart cells? Researchers took skin cells from two male patients with heart failure, a 51 and 61-year-old, and genetically reprogrammed them by injecting a cocktail of "transcription factors" and a virus into the nucleus of the skin cell, followed by removing the virus and transcription factors that have been linked to cancerous tumor growth. The goal was to reprogram the cells into human-induced pluripotent stem cells (hiPSCs) that could help repair hearts.

"One of the obstacles to using hiPSCs clinically in humans is the potential for the cells to develop out of control and become tumours," explained Prof Gepstein in using the technique.

Once in stem cell-form, the cells differentiated in a petri dish to become heart muscle cells called cardiomyocytes, which the researchers then combined with heart tissue and cultured them into healthy heart muscle tissue. Within 48 hours, the tissues were beating together.

"The tissue was behaving like a tiny microscopic cardiac tissue comprised of approximately 1000 cells in each beating area," Gepstein said in a statement.

The researchers then transplanted the new human tissue into rats, finding it grafted to the rat's host cardiac tissues. Their research is published in the May 22 issue of the European Heart Journal.

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Skin cells transformed into beating heart tissue, fueling heart failure treatment hopes

CARLSBAD, Calif.--(BUSINESS WIRE)--International Stem Cell Corporation (OTCBB: ISCO) (www.internationalstemcell.com) today announced that several of its leading scientists will present experimental results from three of ISCOs pre-clinical therapeutic programs.

These results not only show the progress we have made in these important programs, but also demonstrate the broad application of human parthenogenetic stem cells in the development of treatments for incurable diseases

Firstly, the application of A9 dopaminergic neurons derived from human parthenogenetic stem cells (hpSC) for the treatment of Parkinsons disease. Demonstrating functional dopaminergic neurons in vivo represents an important milestone towards the goal of creating well characterized populations of cells that could be used to develop a treatment for Parkinsons.

Secondly, the differentiation of hpSC and embryonic stem cells into cornea-like constructs for use in transplantation therapy and the in vitro study of ocular drug absorption. There are approximately ten million people worldwide who are blind as a result of damage to their cornea. Generating human corneas from a pluripotent stem cell source should increase the likelihood that people will receive treatment in the future even in the absence of suitable tissue from eye banks.

Lastly, the in vivo and in vitro characterization of immature hepatocyte derived from hpSC. Such cells could be used to develop a treatment for individuals with a liver that has been damaged by disease or sufferers of genetic disorders that inhibit normal liver function. In both cases, implanting healthy hepatocyte cells could treat the underlying disease and prolong the life of the individual.

These results not only show the progress we have made in these important programs, but also demonstrate the broad application of human parthenogenetic stem cells in the development of treatments for incurable diseases, says Dr. Ruslan Semechkin, Vice President of Research and Development.

The presentations will take place at the 15th Annual Meeting of American Society of Gene and Cell Therapy, in Philadelphia at 3:30 p.m. on Thursday, May 17th.

About International Stem Cell Corporation

International Stem Cell Corporation is focused on the therapeutic applications of human parthenogenetic stem cells (hpSCs) and the development and commercialization of cell-based research and cosmetic products. ISCO's core technology, parthenogenesis, results in the creation of pluripotent human stem cells from unfertilized oocytes (eggs). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenic, homozygous stem cell line that can be a source of therapeutic cells for hundreds of millions of individuals of differing genders, ages and racial background with minimal immune rejection after transplantation. hpSCs offer the potential to create the first true stem cell bank, UniStemCell. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology (www.lifelinecelltech.com), and stem cell-based skin care products through its subsidiary Lifeline Skin Care (www.lifelineskincare.com). More information is available at http://www.internationalstemcell.com or follow us on Twitter @intlstemcell.

To receive ongoing corporate communications, please click on the following link: http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0

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International Stem Cell Corporation Scientists to Present Pre-Clinical Research Results at American Society of Gene ...

CARLSBAD, Calif.--(BUSINESS WIRE)--

International Stem Cell Corporation (OTCBB: ISCO.OB - News) http://www.internationalstemcell.com today announced that the Company has developed new technologies to commercialize the use of human parthenogenetic stem cells (hpSC) to treat human diseases. The methods announced today are capable of producing populations of stem cells and their therapeutically valuable derivatives not only to a higher level of purity but also at a cost that is approximately several times lower than previously reported techniques.

ISCOs research team has developed a new method to derive high-purity populations of neural stem cells (NSC) from hpSC and further differentiate them into dopaminergic neurons. This method is capable of generating sufficient quantities of neuronal cells for ISCOs pre-clinical and clinical studies and is highly efficient as it requires substantially less time and labor in addition to using fewer costly materials than traditional methods. ISCOs technologies make possible the creation of billions of neuronal cells necessary for conducting such studies from a small batch of stem cells.

ISCO has also announced today that it has developed a new high-throughput cell culture method for growing human parthenogenetic stem cells (hpSC) in large quantities. This new technique is easily scalable and can produce the quantities of cGMP grade hpSC necessary for commercial and therapeutic applications.

One of the most challenging issues in commercializing stem cell based treatments is creating high-purity populations of stem cell derivatives at a reasonable cost. I believe the new methods we have developed solve this important problem and help position us for future clinical studies, says Dr. Ruslan Semechkin, Vice President, R&D.

About International Stem Cell Corporation

International Stem Cell Corporation is focused on the therapeutic applications of human parthenogenetic stem cells (hpSCs) and the development and commercialization of cell-based research and cosmetic products. ISCO's core technology, parthenogenesis, results in the creation of pluripotent human stem cells from unfertilized oocytes (eggs). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenic, homozygous stem cell line that can be a source of therapeutic cells for hundreds of millions of individuals of differing genders, ages and racial background with minimal immune rejection after transplantation. hpSCs offer the potential to create the first true stem cell bank, UniStemCell. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology, and stem cell-based skin care products through its subsidiary Lifeline Skin Care (www.lifelineskincare.com). More information is available at http://www.internationalstemcell.com or follow us on Twitter @intlstemcell.

To receive ongoing corporate communications, please click on the following link: http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0.

Forward-looking Statements

Statements pertaining to anticipated developments, the potential benefits of research programs and new manufacturing technologies, and other opportunities for the company and its subsidiaries, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates,") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products and technologies regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligation to update forward-looking statements.

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International Stem Cell Corporation Announces New Stem Cell Manufacturing Technologies to Support its Therapeutic ...

A stem cell breakthrough at UCLA could mark a big step for a biopharmaceutical company to use its proprietary technology to forge partnerships with pharmaceutical companies and other research institutions.

Fibrocell Sciences technology isolates, purifies and multiplies a patients fibroblast cells, connective skin cells that make collagen. In a research collaboration with the company, UCLA used the technology to isolate, identify and increase the number of different skin cell types, which lead to two rare adult stem cell-like subpopulations being identified in adult human skin SSEA3-expressing regeneration-associated cells associated with skin regeneration after injuries and mesenchymal adult stem cells.

The findings could have broad applications for personalized medicine. Currently, adult stem cells are derived from adipose tissue and bone marrow. Using mesenchymal stem cells would be less invasive and could be more efficient. Mesenchymal stem cells are being used in research to develop osteoblasts, or bone cells; chondrocytes, or cartilage cells; and adipocytes, or fat cells.

David Pernock, the chairman and CEO of Fibrocell, said the move could mark a significant step in the companys growth.

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Stem cell collaboration could set stage for company’s growth

By Carolyn Y. Johnson, Globe Staff

Two teams of Boston scientists have developed new ways to turn stem cells into different types of lung tissue, surmounting a major hurdle for scientists trying to harness the power of stem cell biology to study and develop treatments for major lung diseases.

One team then used skin cells from cystic fibrosis patients to create embryonic-like stem cells, then working in lab dishes used those cells to grow tissue that lines the airways and contains a defect responsible for the rare, fatal disease. The technique -- essentially a recipe for growing such lung tissue -- could provide a powerful platform to screen drugs and study the biology of the disease.

Growing lung tissue in the laboratory has long been a goal of stem cell scientists, but has been more technically difficult than growing other types of tissues, such as brain cells or heart cells. Such lung tissue is valuable because it could be used to screen potential drugs and more closely probe the problems that underlie diseases such as asthma, emphysema, and rare genetic diseases. Such techniques may also one day help researchers grow replacement tissues and devise ways to restore or repair injured lung tissue.

A team led by Massachusetts General Hospital researchers created lung tissue from a patient with the genetic mutation that most commonly underlies cystic fibrosis and researchers hope the technique will also be a powerful tool to study other diseases that affect the airway tissue, such as asthma and lung cancer. The other team, led by Boston University School of Medicine scientists, was able to derive cells that form the delicate air sacs of the lung from mouse embryonic stem cells. The team is hoping to refine the recipe for making the cells so that they can be used to derive lung tissue from a bank of 100 stem cell lines of patients with lung disease. Both papers were published Thursday in the journal Cell Stem Cell.

Vertex Pharmaceuticals, a Cambridge biotechnology company, earlier this year received approval for Kalydeco -- the first drug to directly target the underlying cause of cystic fibrosis. That compound was discovered by screening massive numbers of potential drugs against cells engineered to carry the same defect that underlies cystic fibrosis.

We had to use engineered cells, and certainly using more native human cells ... would be potentially beneficial, said Dr. Frederick Van Goor, head of biology for Vertexs cystic fibrosis research program. We had to rely on donor tissue obtained from patients with cystic fibrosis, and its a bit more challenging, because the number of donor lungs you can get and the number of cells you can derive from there are more limited.

Van Goor said it was too soon to say whether the company would use the new technology in screening, but noted that the tests the company had used to determine whether a drug was likely to work against the disease had, in some cases, given scientists false leads. Some molecules that worked on the engineered cells did not work in the complicated biology of the lung.

Its a significant event for the lung field, said Dr. Thiennu Vu, associate professor of medicine at the University of California San Francisco, who was not involved in the research. She added that much work remains before such cells could be used to repair or replace damaged tissue, and even before such cells would necessarily be useful for drug screening. It will be important, she said, to refine the recipe to ensure that the technique yields pure populations of the specific types of functional lung cells.

In the competitive world of science, where credit for being the first to do something is crucially important, the two research teams accomplishments are an unusual example of competitors turning into collaborators -- forging a relationship that both teams felt helped speed up progress.

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Boston scientists grow lung tissue from cystic fibrosis patients’ skin cells

ALBANY, N.Y. Almost halfway through a $600 million state program supporting stem cell research, eight medical schools around New York are reporting progress on projects such as replicating liver cells and eradicating leukemia cells.

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A new report from Associated Medical Schools of New York updates work at the institutions where hundreds of researchers are starting to unravel causes and potential treatments for conditions ranging from autism to heart disease and cancer. Stem cells are self-renewing and have the ability to develop into other types of cells.

The Mount Sinai School of Medicine reported finding a method to transform human skin cells into stem cells and turned differentiated human stem cells into heart cells. Those findings are expected to result in better understanding of how heart disease develops and allow initial testing of new treatments on stem cells before they are used on human subjects.

Dr. Ihor Lemischka, director of the Black Family Stem Cell Institute at Mount Sinai, said recreating heart cells in a dish from a patient with LEOPARD Syndrome, a disease caused by a genetic mutation, has opened ongoing avenues for researching the disease and screening potential drugs.

"It was a major achievement," Lemischka said. The initial work was reported in June 2010 in the journal Nature.

The shared research facility at Mount Sinai supports the work at 80 different labs, Lemischka said.

The Empire State Stem Cell Program was intended to fund projects in early stages, including those that initially have been unable to get federal or private funding. Grants have also been used for capital projects like renovating labs and establishing new stem cell centers.

The Albert Einstein College of Medicine reported replicating liver cells that could help reduce the need for liver transplants using live donors and cadavers.

Dr. Allen Spiegel said 12 new researchers have been hired with state funding at the Bronx school, which also lists anemia, brain disorders, heart disease and obesity among its stem cell research subjects.

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NY medical schools chart progress with stem cells

Source: ISNA, Tehran

Iranian researcher and lecturer Radbod Darabi jointly with his collogues from the University of Minnesota's Lillehei Heart Institute have effectively treated muscular dystrophy in mice using human stem cells derived from a new process which for the first time makes the production of human muscle cells from stem cells efficient and effective.

Radbod Darabi, MD, PhD with Rita Perlingeiro, PhD. (Credit: Image courtesy of University of Minnesota Academic Health Center)

The research outlines the strategy for the development of a rapidly dividing population of muscle-forming cells derived from induced pluripotent (iPS) cells.

IPS cells have all of the potential of embryonic stem (ES) cells, but are derived by reprogramming skin cells. They can be patient-specific, which renders them unlikely to be rejected, and do not involve the destruction of embryos.

This is the first time that human stem cells have been shown to be effective in the treatment of muscular dystrophy.

According to the researchers, there has been a significant lag in translating studies using mouse stem cells into therapeutically relevant studies involving human stem cells.

This lag has dramatically limited the development of cell therapies or clinical trials for human patients.

The latest research from the University of Minnesota provides the proof-of-principle for treating muscular dystrophy with human iPS cells, setting the stage for future human clinical trials.

As the researchers noted one of the biggest barriers to the development of cell-based therapies for neuromuscular disorders like muscular dystrophy has been obtaining sufficient muscle progenitor cells to produce a therapeutically effective response.

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Iranian researcher helps treating muscular dystrophy using stem cells