Creative Medical Health to Recruit Principal Investigator for U.S. Clinical Trial on Use of Stem Cells for Treatment …

PHOENIX--(BUSINESS WIRE)--Creative Medical Health, Inc. (CMH) announced today initiation of efforts to recruit a preeminent U.S. urologist as principal investigator to run a Phase I/II study under FDA jurisdiction assessing efficacy of its patented method of treating erectile dysfunction.

Creative Medical Health, Inc. owns U.S. patent #8,372,797, titled Treatment of Erectile Dysfunction by Stem Cell Therapy, which covers the use of various stem cells for treatment of patients who are resistant to Viagra, Cialis and Levitra. In contrast to pharmaceutical agents, the treatment developed by Creative Medical Health, Inc. involves regenerating the blood vessels and smooth muscle of the penis, thus offering the possibility of permanent regeneration, not a temporary remedy.

The medical procedure involves extracting stem cells from the patients own bone marrow, processing them and subsequent administration into the penis. A peer-reviewed study describing the first patient treated with this procedure may be found at http://www.translational-medicine.com/content/pdf/1479-5876-11-139.pdf.

There are approximately 18 million patients with erectile dysfunction in the USA. Of these, 30% are resistant to pharmaceutical interventions, which represents approximately 5.4 million potential patients that could benefit from our approach, stated Timothy Warbington, CEO of Creative Medical Health, Inc. Given that this patient group has limited alternatives besides costly implants and injections before intercourse, which can be associated with horrific side effects, we believe it is our responsibility to accelerate development of this program in a timely manner.

The use of bone marrow stem cells is currently part of medical practice in bone marrow transplantation, and is currently in advanced clinical trials for conditions including heart failure, peripheral artery disease and stroke. Creative Medical Health, Inc. is the first to patent and subsequently clinically validate the feasibility of applying this form of stem cell therapy to urological conditions.

Investigators interested in collaborating with Creative Medical Health, Inc. should contact Timothy Warbington at CEO@creativemedicalhealth.com.

About Creative Medical Health Inc:

CREATIVE MEDICAL HEALTH, INC. and its wholly owned subsidiaries, in collaboration with leading U.S. universities, physicians and scientists, have developed and tested our patented cutting-edge BIONUTRACEUTICAL(TM) products, stem cell related blood testing services and treatment of various medical conditions with stem cell technology. Our area of concentration is the scientific and evidence-based approach to the approximately $30 billion per year complementary and alternative medicine market in the United States and $250 billion worldwide market. For more information about Creative Medical Health go to http://www.creativemedicalhealth.com.

The statements and products have not been evaluated or approved by the FDA. They are not intended to diagnose, treat, cure or prevent any disease or condition.

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Creative Medical Health to Recruit Principal Investigator for U.S. Clinical Trial on Use of Stem Cells for Treatment ...

Xcelthera Inc Secures First U.S. Patent for Large-Scale Production of High Quality Human Embryonic Stem Cells and …

San Diego, CA (PRWEB) May 08, 2014

Xcelthera Inc, a major innovator in the stem cell research market and one of the first U.S. companies formed for clinical applications of human embryonic stem cell (human ES cell) therapeutic utility for unmet medical needs, and its joint research partner San Diego Regenerative Medicine Institute announced today that the U.S. Patent and Trademark Office (USPTO) has granted Patent No. 8,716,017 entitled, Technologies, Methods, and Products of Small Molecule-Directed Tissue and Organ Regeneration from Human Pluripotent Stem Cells. This newly-issued patent is the first among a portfolio of intellectual property of Xcelthera Inc covering PluriXcel human stem cell technology platform for large-scale production of high quality clinical-grade pluripotent human ES cell lines and their functional human neuronal and heart muscle cell therapy products.

Neurodegenerative and heart diseases are major health problems and cost the worldwide healthcare system more than $500 billion annually. The limited capacity of these two cell systems -- neurons and cardiomyocytes -- for self-repair makes them suitable for stem cell-based neuronal and heart therapies. Nevertheless, to date, the existing markets lack a clinically-suitable human neuronal cell source or cardiomyocyte source with adequate regenerative potential, which has been the major setback in developing safe and effective cell-based therapies for neurodegenerative and heart diseases. Xcelthera proprietary PluriXcel technology allows efficient derivation of clinical-grade human ES cell lines and direct conversion of such pluripotent human ES cells by small molecule induction into a large commercial scale of high quality human neuronal or heart muscle cells, which constitutes clinically representative progress in both human neuronal and cardiac therapeutic products for treating neurodegenerative and heart diseases.

PluriXcel technology of Xcelthera Inc is milestone advancement in stem cell research, offering currently the only available human cell therapy products with the pharmacological capacity to regenerate human neurons and contractile heart muscles that allow restitution of function of the central nervous system (CNS) and heart in the clinic. Through technology license agreement with San Diego Regenerative Medicine Institute, Xcelthera Inc has become the first in the world to hold the proprietary breakthrough technology for large-scale production of high quality clinical-grade pluripotent human ES cell lines and their functional human neuronal and heart cell therapy products for commercial and therapeutic uses.

As neurodegenerative and heart diseases incur exorbitant costs on the healthcare system worldwide, there is a strong focus on providing newer and more efficient solutions for these therapeutic needs. Millions of people are pinning their hopes on stem cell research. PluriXcel technology platform of Xcelthera Inc is incomparable, providing life scientists and clinicians with novel and effective resources to address major health concerns. Such breakthrough stem cell technology has presented human ES cell therapy derivatives as a powerful pharmacologic agent of cellular entity for a wide range of incurable or hitherto untreatable neurodegenerative and heart diseases. Introduction of medical innovations and new business opportunities based on PluriXcel technology will shape the future of medicine by providing pluripotent human ES cell-based technology for human tissue and function restoration, and bringing new therapeutics into the market.

About Xcelthera Inc.

Xcelthera INC (http://www.xcelthera.com) is a new biopharmaceutical company moving towards clinical development stage of novel and most advanced stem cell therapy for a wide range of neurological and cardiovascular diseases with leading technology and ground-breaking medical innovation in cell-based regenerative medicine. The Company was recently incorporated in the state of California to commercialize the technologies and products developed, in part, with supports by government grants to the founder, by San Diego Regenerative Medicine Institute (SDRMI), an non-profit 501C3 tax-exempt status independent biomedical research institute that is interested in licensing its PATENT RIGHTS in a manner that will benefit the public by facilitating the distribution of useful products and the utilization of new processes, but is without capacity to commercially develop, manufacture, and distribute any such products or processes. Xcelthera is a major innovator in the stem cell research market and one of the first companies formed for clinical applications of human embryonic stem cell (human ES cell) therapeutic utility for unmet medical needs. The Company is the first to hold the proprietary breakthrough technology for large-scale production of high quality clinical-grade pluripotent human ES cell lines and their functional human neuronal and heart muscle cell therapy products for commercial and therapeutic uses. The Company owns or has exclusive rights in a portfolio of intellectual property or license rights related to its novel PluriXcel human stem cell technology platforms and Xcel prototypes of human stem cell therapy products. The inception of Xcelthera is driven by the urgent need for clinical translation of human ES cell research discoveries and innovations to address unmet medical challenges in major health problems. Xcelthera breakthrough developments in human ES cell research dramatically increase the overall turnover of investments in biomedical sciences to optimal treatment options for a wide range of human diseases. The overall strategy of the Company is to use cutting-edge human stem cell technology to develop clinical-grade functional human neural and cardiac cell therapy products from pluripotent human ES cells as cellular medicine or cellular drugs to provide the next generation of cell-based therapeutic solutions for unmet medical needs in world-wide major health problems. The Company is currently offering Series A Convertible Preferred Stock to accredited investors through equity crowdfunding to raise fund for its pre-IPO business operation and filing confidential IPO as an emerging growth company according to the JOBS Act to create a public market for its common stock and to facilitate its future access to the public equity market and growth of the Company.

Visit Xcelthera Inc. at http://www.xcelthera.com.

For more information or investment opportunity about Xcelthera series A round, please contact: Xuejun H Parsons, PhD, Chief Executive Officer Xcelthera Inc. http://www.xcelthera.com 888-706-5396 or 858-243-2046 investors(at)xcelthera.com or parsons(at)xcelthera.com

About San Diego Regenerative Medicine Institute

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Xcelthera Inc Secures First U.S. Patent for Large-Scale Production of High Quality Human Embryonic Stem Cells and ...

Study Urges Caution in Stem Cell Clinical Trials for Heart Attack Patients

CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER. (PRNewsFoto/Cincinnati Children's Hospital Medical Center)

CINCINNATI, May 7, 2014 /PRNewswire-USNewswire/ --A new study in Nature challenges research data that form the scientific basis of clinical trials in which heart attack patients are injected with stem cells to try and regenerate damaged heart tissue.

Researchers at Cincinnati Children's Hospital Medical Center and the Howard Hughes Medical Institute (HHMI), report May 7 that cardiac stem cells used in ongoing clinical trials which express a protein marker called c-kit do not regenerate contractile heart muscle cells at high enough rates to justify their use for treatment.

Including collaboration from researchers at Cedars-Sinai Heart Institute in Los Angeles and the University of Minnesota's Lillehei Heart Institute, the study uncovers new evidence in what has become a contentious debate in the field of cardiac regeneration, according to Jeffery Molkentin, PhD, study principal investigator and a cardiovascular molecular biologist and HHMI investigator at the Cincinnati Children's Heart Institute.

"Our data suggest any potential benefit from injecting c-kit-positive cells into the hearts of patients is not because they generate new contractile cells called cardiomyocytes," Molkentin said. "Caution is warranted in further clinical testing of this method until the mechanisms in play here are better defined or we are able to dramatically enhance the potential of these cells to generate cardiomyocytes."

Numerous heart attack patients have already been treated with c-kit-positive stem cells that are removed from healthy regions of a damaged heart then processed in a laboratory, Molkentin explained. After processing, the cells are then injected into these patients' hearts. The experimental treatment is based largely on preclinical studies in rats and mice suggesting that c-kit-positive stem cells completely regenerate myocardial cells and heart muscle. Thousands of patients have also previously undergone a similar procedure for their hearts but with bone marrow stem cells.

Molkentin and his colleagues report those previous preclinical studies in rodents do not reflect what really occurs within the heart after injury, where internal regenerative capacity is almost non-existent. Molkentin also said that combined data from multiple clinical trials testing this type of treatment show most patients experienced a roughly 3-5 percent improvement in heart ejection fraction a measurement of how forcefully the heart pumps blood. Data in the current Nature study suggest this small benefit may come from the ability of c-kit-positive stem cells in heart to cause the growth of capillaries, which improves circulation within the organ, but not by generating new cardiomyocytes.

"What we show in our study is that c-kit-positive stem cells from the heart like to make endothelial cells that form capillaries. But in their natural environment in the heart, these c-kit positive cells do not like to make cardiomyocytes," Molkentin said. "They will produce cardiomyocytes, but at rates so low roughly one in every 3,000 cells it becomes meaningless."

The c-kit protein is expressed on the surface of progenitor cells originally identified in bone marrow. These c-kit expressing cells can generate multiple different cell types that are destined to help form specific organ tissues or other parts of the body. Given its presence in bone marrow, c-kit cells are also involved in the production of different types of immune system cells.

Researchers in the current study worked with two lines of genetically bred mice to see how efficiently c-kit-positive cardiac progenitor cells would regenerate cardiomyocytes in the hearts of the animals. The authors measured heart cell regeneration rates during the animals' embryonic development, during aging and after myocardial infarction (heart attack).

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Molecular Biology Chair Eric Olson to Head to New Hamon Center for Regenerative Medicine

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Newswise DALLAS May 7, 2014 UT Southwestern Medical Center today announced the formation of the Hamon Center for Regenerative Science and Medicine led by Dr. Eric Olson, Chairman of the Department of Molecular Biology.

This new Center was made possible by a $10 million endowment gift from the Hamon Charitable Foundation. It is being established to promote discoveries that will provide new approaches to healing and regeneration, including advances in stem cell biology, tissue engineering, and organ fabrication.

We look forward to the emergence of the Hamon Center as a leading source of transformative insights into regenerative science and medicine, said Dr. Daniel K. Podolsky, President of UT Southwestern. We are delighted to be able to announce this very generous gift from the Hamon Foundation, the establishment of the Hamon Center for Regenerative Science and Medicine, and this important new role for Dr. Olson.

Dr. Olsons work has produced new insights into heart development and regeneration. His work has illuminated a detailed genetic model for heart development that provides a framework for how these genes function in normal and abnormal heart development. These advances provide a basis for the development of new approaches to the treatment and prevention of cardiac defects in infants and cardiac repair in adults, including several therapeutics already in development.

We all know what degeneration is. Thats what happens with age. Regeneration is the opposite. It centers on how to rejuvenate aged and diseased tissues, said Dr. Olson. The goal of this Center is to understand the basic mechanisms for tissue and organ formation, and then to use that knowledge to regenerate, repair, and replace tissues damaged by aging and injury.

Under Dr. Olsons leadership, the Hamon Center will both foster collaborative interactions among existing faculty and, with its appointing authority, recruit junior and senior new faculty. In addition, the Center will support new core facilities, expanded biobank activities, and the development of new training and educational activities related to regenerative science and medicine.

Dr. Olsons work has been widely recognized by numerous awards and honors, including his election to the National Academy of Sciences, the Institute of Medicine, and the American Academy of Arts and Sciences. More recently, he received the Passano Award in 2012, the Research Achievement Award from the International Society for Heart Research in 2013, and also in 2013, the March of Dimes Prize in Developmental Biology.

Dr. Olson has been a member of the UTSouthwestern community since he was recruited in 1995 to be the founding Chair of the Department of Molecular Biology. He holds the Annie and Willie Nelson Professorship in Stem Cell Research, the Pogue Distinguished Chair in Research on Cardiac Birth Defects, and the Robert A. Welch Distinguished Chair in Science.

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Accusations pile up amid Japans stem-cell controversy

The Asahi Shimbun via Getty Images

The investigative committee that said a RIKEN scientist had committed misconduct, presenting its findings on 1 April in Tokyo. From left to right: Shunsuke Ishii, Atsushi Iwama, Haruhiko Koseki, Yoichi Shinkai, Tetsuya Taga and Jun Watanabe

Four of the six members of a Japanese committee that found misconduct in studies claiming to demonstrate a simple technique to produce stem cells are now facing allegations of irregularities in their own published work.

The allegations complicate an already murky controversy over the technology, known as stimulus-triggered acquisition of pluripotency (STAP). Stem-cell biologist Haruko Obokata of the RIKEN Center for Developmental Biology in Kobe, Japan, described in two Nature papers published on 30 January1, 2 how she and her colleagues had reprogrammed mouse cells into stem cells by soaking them in acid or applying physical pressure.

Within weeks, numerous problems with the papers surfaced, including manipulated and duplicated images. On 1 April Obokata was charged with misconduct by a RIKEN investigative committee comprising five scientists and a lawyer. Obokata appealed the judgement on 8 April, and the committee was given 50 days to consider that appeal. On 6 May, the Japanese media reported that the investigative committee decided to deny Obokata's request for a re-examination. Obokata can no longer appeal the finding through the organization's appeal system. RIKEN will now begin the process of deciding penalties to Obokata and her co-authors.

On 25 April, the head of the investigation committee, Shunsuke Ishii, resigned from the committee after manipulated images from two of his earlier papers were posted on the Internet. Ishii maintains that neither of the problems amount to fraud, and he posted photos from the original laboratory notebooks to support that point. RIKEN launched a preliminary inquiry into his papers.

More trouble arose for RIKEN on 30 April, when a whistle-blower alleged problems in the images of papers co-authored by two other RIKEN researchers on the committee, Haruhiko Koseki and Yoichi Shinkai. RIKEN launched a preliminary investigation into the allegations that same day. Satoru Kagaya, a RIKEN spokesman, says that the whistle-blower, whose name RIKEN will not reveal, alleges that four papers from Koseki, published between 2003 and 2011, and one paper by Shinkai, published in 2005, contain data that were manipulated in one or two spots.

Meanwhile, also on 30 April, a journalist from the daily newspaper Asahi Shimbun notified Tokyo Medical and Dental University of allegations regarding Tetsuya Taga, the university's president and another one of the RIKEN panel investigators. Two papers on neural stem cells co-authored by Taga, from 2004 and 2005, each had two illustrations that, the journalist said, appeared to be manipulations.

The next day, the university launched a preliminary enquiry headed by four university administrators. After one day of deliberation, which included a discussion with Taga and two co-authors and an examination of laboratory notebooks, the university concluded that Taga was not guilty of misconduct. A university spokesperson declined to say whether the university found no manipulations at all or whether they found manipulations but deemed them not to be misconduct. The spokesperson said a clarification of that issue will be posted online tomorrow.

Obokatas lawyer has stated that the problems in the committee members' papers are akin to those found in Obokatas errors, but not fraud.

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Accusations pile up amid Japans stem-cell controversy

Service dog receives cutting-edge stem cell therapy

A service dog that has come from the brink of death and back was in Terry on Wednesday to receive cutting-edge stem cell therapy.

Davis Hawn said his dog, Booster, saved his life and now he's working to return the favor.

"With Booster by my side, I greet each day knowing we can change the world for the better," Hawn said.

Together, Hawn and Booster helped foster international relations by appearing on TV in Cuba. They reassured Thai orphans infected with the HIV virus that life will be OK and they are loved. The list of accomplishments continued to grow until Booster developed hip dysplasia.

"When Booster couldn't get off the floor, I couldn't get out of bed," said Hawn, who suffers from depression. "Just as assuredly as God put Booster into my life, He again answered the call when I read about the modern day marvel of stem-cell implantation."

Medivet America, a global leader in veterinary science with more than 1,000 clinics in 28 countries, learned of Booster's plight and jumped in to help.

"They arranged to perform a procedure in which they injected Booster's own stem cells into his hips and got him back up and running again," Hawn said. "When I went to pay the bill, they refused to accept payment. I like to say that God paid the bill."

In January 2013, Booster again faced a health battle. He was diagnosed with squamous cell carcinoma and given three weeks to live. An aggressive tumor had eaten through Booster's skull cap and left him writhing in pain. In an effort to save Booster's life, Hawn moved to Florida where the University of Florida operated on Booster and a referral clinic performed radiation therapy.

The University of Minnesota took a piece of the tumor that was removed from Booster and used it to developed the first vaccine for squamous cell carcinoma in dogs.

Booster is now a cancer survivor.

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Service dog receives cutting-edge stem cell therapy

Top 10 Stem Cell Treatment Facts | Closer Look

Many clinics that are offering stem cell treatments make claims about what stem cells can and cannot do that are not supported by our understanding of science. The information on this page corrects some of the misinformation that is being widely circulated.

There are many different types of stem cells that come from different placesin the body or are formed at different times in our lives. These include embryonic stem cells that exist only at the earliest stages of development and various types of tissue-specific or adult stem cells that appear during fetal development and remain in our bodies throughout life.

Our bodies use different types of tissue-specific stem cells to fit a particular purpose. Tissue-specific stem cells are limited in their potential and largely make the cell types found in the tissue from which they are derived. For example, the blood-forming stem cells (or hematopoietic stem cells) in the bone marrow regenerate the blood, while neural stem cells in the brain make brain cells. A neural stem cell wont spontaneously make a blood cell and likewise a hematopoietic stem cell wont spontaneously make a brain cell. Thus, it is unlikely that a single cell type could be used to treat a multitude of unrelated diseases that involve different tissues or organs. Be wary of clinics that offer treatments with stem cells thatoriginate from a part of the body that is different from the part being treated.

Read more about differentTypes of Stem Cells

As described above, each type of stem cell fulfills a specific function in the body and cannot be expected to make cell types from other tissues. Thus, it is unlikely that a single type of stem cell treatment can treat multiple unrelated conditions, such as diabetes and Parkinsons disease. The underlying causes are very different and different cell types would need to be replaced to treat each condition. It is critical that the cell type used as a treatment be appropriate to the specific disease or condition.

Embryonic stem cells may one day be used to generate treatments for a range of human diseases. However, embryonic stem cells themselves cannot directly be used for therapies as they would likely cause tumors and are unlikely to become the cells needed to regenerate a tissue on their own. They would first need to be coaxed to develop into specialized cell types before transplantation. A major warning sign that a clinic may not be credible is when treatments are offered for a wide variety of conditions but rely on a single cell type.

The range of diseases where stem cell treatments have been shown to be beneficial in responsibly conducted clinical trials is still extremely restricted. The best defined and most extensively used is blood stem cell transplantation to treat diseases and conditions of the blood and immune system, or to restore the blood system after treatments for specific cancers. Some bone, skin and corneal diseases or injuries can be treated with grafting of tissue that depends upon stem cells from these organs. These therapies are also generally accepted as safe and effective by the medical community.

There are three main reasons why a person might feel better that are unrelated to the actual stem cell treatment: the placebo effect, accompanying treatments, and natural fluctuations of the disease or condition. The intense desire or belief that a treatment will work can cause a person to feel like it has and to even experience positive physical changes, such as improved movement or less pain. This phenomenon is called the placebo effect. Even having a positive conversation with a doctor can cause a person to feel improvement. Likewise, other techniques offered along with stem cell treatmentsuch as changes to diet, relaxation, physical therapy, medication, etc.may make a person feel better in a way that is unrelated to the stem cells. Also, the severity of symptoms of many conditions can change over time, resulting in either temporary improvement or decline, which can complicate the interpretation of the effectiveness of treatments. These factors are so widespread that without testing in a controlled clinical study, where a group that receives a treatment is carefully compared against a group that does not receive this treatment, it is very difficult to determine the real effect of any therapy. Be wary of clinics that measure or advertise their results primarily through patient testimonials.

Science, in general, is a long and involved process. Understanding what goes wrong in disease or injury and how to fix it takes time. New ideas have to be tested first in a research laboratory, and many times the new ideas dont work. Even once the basic science has been established, translating it into an effective medical treatment is a long and difficult process. Something that looks promising in cultured cells may fail as a therapy in an animal model and something that works in an animal model may fail when it is tried on humans. Once therapies are tested in humans, ensuring patient safety becomes a critical issue and this means starting with very few people until the safety and side effects are better understood.

If a treatment has not been carefully designed, well studied and gone through the necessary preclinical and clinical testing, it is unlikely to have the desired effect. Even more concerning is that it may prove to make the condition worse or have dangerous side effects. SeeHow Science Becomes Medicine

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Top 10 Stem Cell Treatment Facts | Closer Look

Pushing the boundaries of stem cells

PUBLIC RELEASE DATE:

7-May-2014

Contact: Lucia Lee NewsMedia@mssm.edu 212-241-9200 The Mount Sinai Hospital / Mount Sinai School of Medicine

(NEW YORK May 7) Adults suffering from diseases such as leukemia, lymphoma, and other blood-related disorders may benefit from life-saving treatment commonly used in pediatric patients. Researchers at the Icahn School of Medicine at Mount Sinai have identified a new technique that causes cord blood (CB) stems cells to generate in greater numbers making them more useful in adult transplantation.

The study, published in the May issue of The Journal of Clinical Investigation, looked at ways to expand the number of hematopoietic stem cells (HSC) in the laboratory required to replenish and renew blood cells. Cord blood stem cells have the ability to rapidly divide in the presence of combinations of growth factors but they often lose their marrow-repopulating potential following cell division. Researchers looked at ways to overcome this limitation by inducing a genetic program by which a stem cell retains its full functional properties after dividing in the laboratory.

"Cord blood stem cells have always posed limitations for adult patients because of the small number of stem cells present in a single collection," said Pratima Chaurasia, PhD, Assistant Professor of Medicine at the Tisch Cancer Institute at Mount Sinai. "These limitations have resulted in a high rate of graft failure and delayed engraftment in adult patients."

Researchers used a technique called epigenetic reprogramming which reshaped cell DNA by treating cells with a combination of histone deacetylase inhibitors (HDACI) and valproic acid. The VPA-treated cells produced a greater number of repopulating cells, and established multilineage hematopoiesis in primary, secondary and tertiary immune-deficient mice.

"We're excited by these results. The findings have important implications for patients battling blood cancers and the difference between success and failure of life saving stem cell transplants." added Ronald Hoffman, MD, Albert A. and Vera G. List Professor of Medicine, Director of Myeloproliferative Disorders Research Program at the Tisch Cancer Institute at Mount Sinai.

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This study was supported by a New York Stem Cell Science grant from the Empire State Stem Cell Board, whose mission is to foster a strong stem cell research community in New York State and to accelerate the growth of scientific knowledge about stem cell biology and the development of therapies and diagnostic methods under the highest ethical, scientific, and medical standards for the purpose of alleviating disease and improving human health.

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Pushing the boundaries of stem cells

One step closer to cell reprogramming

20 hours ago Cells with activated Wnt can no longer be reprogrammed (in green) are located on the periphery; cells that can be reprogrammed are aggregated anad can be seen in the center of the image (in red) Credit: CRG

In 2012, John B. Gurdon and Shinya Yamakana were awarded the Nobel Prize in medicine for discovering that adult cells can be reprogrammed into pluripotent ones (iPS); the cells obtained are capable of behaving in a similar way to embryonic stem cells, and hence have enormous potential for regenerative medicine.

However, although there are many research groups around the world studying this process, it is still not completely understood, it is not totally efficient, and it is not safe enough to be used as the basis for a new cell therapy.

Now, researchers at the Centre for Genomic Regulation (CRG) in Barcelona have taken a very important step towards understanding cell reprogramming and its efficiency: they have discovered the key role of the Wnt signalling pathway in transforming adult cells into iPS cells.

"Generally, transcription factors are used to try to increase or decrease the cell reprogramming process. We have discovered that we can increase the efficiency of the process by inhibiting the Wnt route", explains Francesco Aulicino, a PhD student in the Reprogramming and Regeneration group, led by Maria Pia Cosma and co-author of the study that has just been published in Stem Cell Reports.

The Wnt signaling pathway is a series of biochemical reactions that are produced in cells. In frogs or lizards, for example, these reactions are those that allow their extremities to regenerate if the animal suffers an injury. Although in general, humans and mammals have lost this regenerative capacity, the Wnt pathway is involved in numerous processes during embryonic development and cell fusion.

As it is in reprogramming. The researchers have studied how the Wnt route behaves throughout the entire process of transforming cells into iPS cells, which usually lasts two weeks. It is a very dynamic process that produces oscillations from the pathway, which is not active all the time. "We have seen that there are two phases and that in each one of them, Wnt fulfils a different function. And we have shown that by inhibiting it at the beginning of the process and activating it at the end we can increase the efficiency of reprogramming and obtain a larger number of pluripotent cells", indicates Ilda Theka, also a PhD student in Pia Cosma's group and a co-author of the article.

To artificially control the pathway, the group has employed a chemical molecule, Iwp2, which is a Wnt secretion inhibitor that does not permanently alter the cells, something which other research into reprogramming using different factors has still has not been able to acheive.

They have also seen that the exact moment when the Wnt pathway is activated is crucial. Doing it too early, makes the the cells begin to differentiate, for example into neurones or endodermal cells, and they are not reprogrammed.

"It is a very important and an innovative advance in the field of cell reprogramming, because until now this was a very inefficient process. There are many groups trying to understand the mechanism by which adult cells become pluripotent, and what blocks that process and makes only a small percentage of cells end up being reprogrammed. We are providing information on why it happens", says Theka.

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One step closer to cell reprogramming