Patient dies during procedure

(CNN) -

A Florida cardiologist could have his medical license revoked by state authorities who have accused him of performing illegal stem cell therapy on a patient who died during the procedure.

Florida's Department of Health ordered the emergency suspension of Zannos Grekos' medical license Wednesday, accusing the Bonita Springs doctor of violating an emergency order against using stem cell treatments in Florida and causing the death of an unidentified elderly patient. Grekos can appeal the order.

According to the license suspension order, Grekos performed a stem cell treatment this month on the patient, who was suffering from pulmonary hypertension and pulmonary fibrosis. Both diseases restrict blood flow to the heart.

"During said stem cell treatment, patient R.P. suffered a cardiac arrest and died," the suspension order said.

CNN first investigated Grekos' activities in 2009, when he said he was using stem cell therapy for a company called Regenocyte Therapeutic. His profile, listed on the company's website, describes Grekos as having "extensive experience in the field of stem cell therapy" and says he "was recently appointed to the Science Advisory Board of the United States' Repair Stem Cell Institute."

At the time of CNN's interview, Grekos said he extracted stem cells from patients and then sent the blood to Israel for laboratory processing. That processing, he said, resulted in "regenocytes," which he said would help heal crippling diseases, mostly associated with lung problems.

The president of the International Society of Stem Cell Research, Dr. Irving Weissman, told CNN at the time that "there is no such cell."

"There is nothing called a regenocyte," he said.

After CNN's initial report, Grekos said the name was "advertising" and was not intended to be scientific.

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Patient dies during procedure

Surgeons Urge Caution: Stem Cell Treatments Untested in Aesthetic Surgery

Doctors Haeck, Eaves, and Rohrich write joint ASAPS/ASPS statement calling for more research into stem cell facelift and stem cell breast augmentation.

Dallas, TX (PRWEB) February 22, 2012

There is little evidence to support the safety and effectiveness of procedures, equipment and treatments that have been advertised using adult stem cells for aesthetic reconstruction, including plastic surgery and facial rejuvenation, according to physicians writing in Plastic and Reconstructive Surgery.

Dr. Rod J. Rohrich, chairman of the Department of Plastic Surgery at UT Southwestern Medical Center and editor-in-chief of the journal, published a position statement on “stem cell facelifts” and “stem cell breast augmentation,” also known as “natural breast augmentation.” Dr. Felmont F. Eaves III of Chapel Hill, N.C., and Dr. Phillip C. Haeck of Seattle, Wash.,collaborated on the statement on behalf of the American Society for Aesthetic Plastic Surgery (ASAPS) and the American Society of Plastic Surgeons (ASPS).

“There are encouraging data from studies in laboratories to suggest that the use of adult stem cells is a very promising field and may produce beneficial medical therapies to treat a variety of diseases,” the doctors said in the statement. They emphasized that there is a lack of consistency in the way stem cell facelift procedures are performed, and pointed out that many procedures are being advertised by physicians who are not board-certified for this type of treatment, and devices being sold for aesthetic stem cell treatments have not been approved for human use in the U.S.

In the report, the doctors encourage their peers to continue reporting clinic results and experimental research to peer-reviewed plastic surgery journals to both promote good science and to foster safety and best practices for stem cell use in aesthetic procedures. “Much more research needs to be conducted before any definitive statements can be made,” the report said. “[Until then,] stem cell based procedures should be performed in compliance with FDA regulatory guidelines.”

Dr. Rohrich said many of the advertisements claiming stem cells can aid in restoring facial and body youthfulness come from outside the U.S. “Further direct, approved clinical research is needed to validate those claims,” he said, “but the future is potentially bright for the use of adult stem cells in both plastic surgery and facial rejuvenation, as well as in medical procedures, such as restoring nerve and brain damage resulting from trauma or cancer, as well as reversing the severe effects of auto immune disease.”

To read the complete joint ASAPS/ASPS position statement on stem cell use in aesthetic surgery, including stem cell facelifts and natural breast augmentation, visit the ASPS, at their website.

About Rod J. Rohrich, M.D., F.A.C.S.
Dr. Rod J. Rohrich holds the Betty and Warren Woodward Chair in Plastic and Reconstructive Surgery at UT Southwestern Medical Center in Dallas, Texas. He also holds the UT Southwestern Medical Center Crystal Charity Ball Distinguished Chair in Plastic Surgery. He is a graduate of the Baylor College of Medicine with high honors, with residencies at the University of Michigan Medical Center and fellowships at the Massachusetts General Hospital/Harvard (hand/microsurgery) and Oxford University (pediatric plastic surgery). He has served as president of the American Society of Plastic Surgeons. He repeatedly has been selected by his peers as one of America's best doctors, and twice has received one of his profession's highest honors, the Plastic Surgery Educational Foundation Distinguished Service Award, which recognizes his contributions to education in his field. Dr. Rohrich participates in and has led numerous associations and councils for the advancement of plastic and reconstructive surgery. He is a native of North Dakota. He is married to Dr. Diane Gibby, also a plastic surgeon. They live in Texas with their two children.

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Surgeons Urge Caution: Stem Cell Treatments Untested in Aesthetic Surgery

Stem Cell Clinical Trial for Heart Failure: Eduardo Marban – CIRM Spotlight on Disease – Video

21-12-2011 10:03 CIRM has funded a $5.5 million Disease Team to develop a follow on clinical trial that uses a patient's own heart stem cells to regenerate scarred tissue damaged by a heart attack. The team is led by Eduardo Marban, MD, PhD, Director of the Cedars-Sinai Heart Institute. Marban presented the team's latest progress at the December 8th, 2011 CIRM Governing Board meeting. Fred Lesikar, a participant in a current trial, also spoke to Board and described the dramatic improvement he's experienced since receiving his heart stem cells two years ago. The speakers were introduced by Shlomo Melmed, MD, and Jonathan Thomas, PhD, JD. Melmed is a CIRM Governing Board member and Senior Vice-President for Academic Affairs and Dean of the Medical Faculty at Cedars-Sinai. Thomas is Chair of the CIRM Governing Board.

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Stem Cell Clinical Trial for Heart Failure: Eduardo Marban - CIRM Spotlight on Disease - Video

Huntington's Disease: New Hope from Stem Cell Therapies

(Part 2 of 5) Vicki Wheelock, MD, spoke at the "Spotlight on Huntington's Disease," an educational event presented at the CIRM Governing Board meeting on March 11, 2010. Wheelock is a clinical professor in the department of neurology within the University of California, Davis Health System. She was introduced by Claire Pomeroy, MD, MBA The CIRM-hosted event was presented in partnership with UC Davis at the California State Capitol Building

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Huntington's Disease: New Hope from Stem Cell Therapies

Stem Cell Transplant India,Bone Marrow Transplant India,Sickle Cell Anemia Treatment India

Center for Bone Marrow Transplantation, Bangalore, India was established in October 2004 with a vision to make this treatment affordable to the common man. Since then the unit has completed more than 125 stem cell transplants till date with approximately 100 of them being allogeneic stem cell transplants.

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Stem Cell Transplant India,Bone Marrow Transplant India,Sickle Cell Anemia Treatment India

Parkinson's Disease: Spotlight on Stem Cell Research – Jeff Bronstein

(Part 1 of 3) Jeff Bronstein, MD, Ph.D., spoke at the "Spotlight on Parkinson's Disease," an educational event presented at the CIRM Governing Board meeting on May 7, 2008. Bronstein presented an overview of Parkinson's disease and discussed how stem cell research provides hope for finding new Parkinson's disease therapies.

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Parkinson's Disease: Spotlight on Stem Cell Research - Jeff Bronstein

Alzheimer's Disease: Spotlight on Stem Cell Research – Rod Shankle

(Part 3 of 4) Rodman Shankle, MD spoke at the "Spotlight on Alzheimer's disease", an educational event presented at the CIRM Governing Board meeting on December 10, 2008. Shankle reviewed clinical data, which indicates that stem cells from the fat pad of the intestines have the capacity to repair damaged brain tissue found in Alzheimer's disease and other neurological disorders.

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Alzheimer's Disease: Spotlight on Stem Cell Research - Rod Shankle

Medistem Achieves Important ERC Stem Cell Clinical Trial Milestone

SAN DIEGO, CA--(Marketwire -06/04/12)- Medistem Inc. (MEDS) announced today positive safety data from the first 5 patients enrolled in the Non-Revascularizable IschEmic Cardiomyopathy treated with Retrograde COronary Sinus Venous DElivery of Cell TheRapy (RECOVER-ERC) trial. The clinical trial uses the company's "Universal Donor" Endometrial Regenerative Cells (ERC) to treat Congestive Heart Failure (CHF).

According to the study design, after 5 patients enter the trial, they must be observed for a two month time period before additional patients are allowed to enter the study. Patient data was analyzed by the study's independent Data Safety Monitoring Board (DSMB), which concluded that based on lack of adverse effects, the study be allowed to continue recruitment.

"Medistem is developing a treatment for CHF that uses a 30-minute catheter-based procedure to administer the ERC stem cell into the patients' hearts. The achievement of 2 month patient follow-up with no adverse events is a strong signal for us that our new approach to this terrible condition is feasible," said Thomas Ichim, CEO of Medistem.

The RECOVER-ERC trial will treat a total of 60 patients with end-stage heart failure with three concentrations of ERC stem cells or placebo. The clinical trial is being conducted by Dr. Leo Bockeria, Chairman of the Backulev Centre for Cardiovascular Surgery, in collaboration with Dr. Amit Patel, Director of Clinical Regenerative Medicine at University of Utah.

"As a professional drug developer, I am very optimistic of a stem cell product that can be used as a drug. The ERC stem cell can be stored frozen indefinitely, does not need matching with donors, and can be injected in a simple 30-minute procedure into the heart," said Dr. Sergey Sablin, Vice President of Medistem and co-founder of the multi-billion dollar NASDAQ company Medivation.

Currently patients with end-stage heart failure, such as the ones enrolled in the RECOVER-ERC study, have no option except for heart transplantation, which is limited by side effects and lack of donors. In contrast to other stem cells, ERC can be manufactured inexpensively, do not require tissue matching, and can be administered in a minimally-invasive manner. Animal experiments suggest ERC are more potent than other stem cell sources at restoring heart function. The FDA has approved a clinical trial of ERC in treatment of critical limb ischemia in the USA.

About Medistem Inc. Medistem Inc. is a biotechnology company developing technologies related to adult stem cell extraction, manipulation, and use for treating inflammatory and degenerative diseases. The company's lead product, the endometrial regenerative cell (ERC), is a "universal donor" stem cell being developed for critical limb ischemia and heart failure. A publication describing the support for use of ERC for this condition may be found at http://www.translational-medicine.com/content/pdf/1479-5876-6-45.pdf.

Cautionary Statement This press release does not constitute an offer to sell or a solicitation of an offer to buy any of our securities. This press release may contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Future events and actual results could differ materially from those set forth in, contemplated by, or underlying the forward-looking information. Factors which may cause actual results to differ from our forward-looking statements are discussed in our Form 10-K for the year ended December 31, 2007 as filed with the Securities and Exchange Commission.

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Medistem Achieves Important ERC Stem Cell Clinical Trial Milestone

CEO of stem cell company responds to FDA warning letter

The head of a stem cell company has responded to a warning letter issued by the U.S. Food and Drug Administration that cites several violations at the company that derives stem cells from adipose tissue or body fat.

Dr. Steven Victor of IntelliCell BioSciences said it would be moving to a new facility next month that it believes will address the current good manufacturing practice issues referred to in the warning letter It has also hired consultants with FDA-compliance experience that will help bring its new facilities in compliance with the FDA. Victor added that the company will address all of the FDAs observations on April 3.

The New York company received a warning letter dated March 13 that was published on the FDAs website yesterday. The letter said that the process that the company uses to produce stem cells from adipose tissue did not meet the FDAs definition of minimal manipulation for structural tissue such as adipose tissue.

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CEO of stem cell company responds to FDA warning letter

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

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 ...

Cell transplantation of lung stem cells has beneficial impact for emphysema

Public release date: 4-Jun-2012 [ | E-mail | Share ]

Contact: David Eve Celltransplantation@gmail.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Tampa, Fla. (June 4, 2012) When autologous (self-donated) lung-derived mensenchymal stem cells (LMSCs) were transplanted endoscopically into 13 adult female sheep modeled with emphysema, post-transplant evaluation showed evidence of tissue regeneration with increased blood perfusion and extra cellular matrix content. Researchers concluded that their approach could represent a practical alternative to conventional stem cell-based therapy for treating emphysema.

The study is published in Cell Transplantation (21:1), now freely available on-line at http://www.ingentaconnect.com/content/cog/ct/.

"Mensenchymal stem cells are considered for transplantation because they are readily available, highly proliferative and display multi-lineage potential," said study corresponding author Dr. Edward P. Ingenito of the Brigham and Women's Hospital Division of Pulmonary and Critical Care Medicine. "Although MSCs have been isolated from various adult tissues - including fat, liver and lung tissues - cells derived from bone marrow (BM) have therapeutic utility and may be useful in treating advanced lung diseases, such as emphysema."

However, according to the authors, previous transplantation studies, many of which used an intravenous delivery method, have shown that BM-MSCs have been only marginally successful in treating lung diseases. Further, therapeutic responses in those studies have been limited to animal models of inflammatory lung diseases, such as asthma and acute lung injury.

To try and answer the questions surrounding the utility of BM-MSCs for treating advanced emphysema, a disease characterized by tissue destruction and loss of lung structural integrity, for this study the researchers isolated highly proliferative, mensenchymal cells from adult lung parenchyma (functional tissue) (LMSCs) and used an endoscopic delivery system coupled with a scaffold comprised of natural extracellular matrix components.

"LMSCs display efficient retention in the lung when delivered endobronchially and have regenerative capacity through expression of basement membrane proteins and growth factors," explained Dr. Ingenito.

However, despite the use of autologous cells, only a fraction of the LMSCs delivered to the lungs alveolar compartment appeared to engraft. Cell death likely occurred because of the failure of LMSCs to home to and bind within their niche, perhaps because the niche was modified by inflammation or fibrosis. These cells are attachment-dependent and failure to attach results in cell death."

Their findings did suggest, however, that LMSCs were capable of contributing to lung remodeling leading to documented functional improvement rather than scarring 28 days post transplantation.

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Cell transplantation of lung stem cells has beneficial impact for emphysema

:: 01, Mar 2012 :: A*STAR SCIENTISTS MAKE GROUNDBREAKING DISCOVERY ON STEM CELL REGULATION

MEDIA RELEASE

A*STAR Scientists Make Groundbreaking Discovery on Stem Cell Regulation

New link between polyamine levels and embryonic stem cell state deepens our understanding of embryonic stem cell regulation which is a key step in bringing cellular therapies from the laboratory to the clinic.

1. A*STAR scientists have for the first time, identified that precise regulation of polyamine[1] levels is critical for embryonic stem cell (ESC) self-renewal the ability of ESCs to divide indefinitely and directed differentiation. This paper is crucial for better understanding of ESC regulation and was published in the journal Genes & Development on 1st March by the team of scientists from the Institute of Medical Biology (IMB), a research institute under the Agency for Science, Technology and Research (A*STAR).

2. Embryonic stem cells hold great potential for the development of cellular therapies, where stem cells are used to repair tissue damaged by disease or trauma. This is due to their unique ability to renew themselves and differentiate into any specific types of cell in the body. One of the challenges with cellular therapies is ensuring that ESCs are fully and efficiently differentiated into the correct cell type. This study sheds light on understanding how ESCs are regulated, which is essential to overcome these challenges and turn the vision of cell therapies into reality.

3. Using a mouse model, the team of scientists from IMB showed that high levels of Amd1[2], a key enzyme in the polyamine synthesis pathway, is essential for maintenance of the ESC state and self renewal of ESCs. To further demonstrate the critical role of Amd1 in ESC self-renewal, the scientists showed that increasing Amd1 levels led to delayed ESC differentiation. The research also revealed that downregulation of Amd1 was necessary for differentiation of ESCs into neural precursor cells and that Amd1 is translationally regulated by a micro-RNA (miRNA), the first ever demonstration of miRNA-mediated regulation of the polyamine pathway.

4. While the polyamine pathway is well established and polyamines are known to be important in cancer and cell proliferation, their role in ESC regulation until now was unknown. This novel discovery, linking polyamine regulation to ESC biology, came about when the team set up a genome-wide screen to look for mRNAs under translational control in order to identify new regulators of ESC differentiation to neural precursor cells.

6. Dr Leah Vardy, Principle Investigator at the IMB and lead author of the paper, said, The polyamines that Amd1 regulate have the potential to regulate many different aspects of self renewal and differentiation. The next step is to understand in more detail the molecular targets of these polyamines both in embryonic stem cells and cells differentiating to different cellular lineages. It is possible that manipulation of polyamine levels in embryonic stem cells through inhibitors or activators of the pathway could help direct the differentiation of embryonic stem cells to more clinically useful cell types.

7. Prof. Birgitte Lane, Executive Director of IMB, said, This is a fine piece of fundamental research that will have breakthrough consequences in many areas and can bring about far-reaching applications. Developing cellular therapies is just one long-term clinical benefit of understanding ESC biology, which can also help develop stem cell systems for disease modeling, developing new drugs as well as a tool for researchers to answer other biological questions.

Notes for editor:

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:: 01, Mar 2012 :: A*STAR SCIENTISTS MAKE GROUNDBREAKING DISCOVERY ON STEM CELL REGULATION

Huntington's Disease – Stem Cell Therapy Potential

Editor's Choice Academic Journal Main Category: Huntingtons Disease Also Included In: Stem Cell Research Article Date: 19 Mar 2012 - 10:00 PDT

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However, according to a study published March 15 in the journal Cell Stem Cell, a special type of brain cell created from stem cells could help restore the muscle coordination deficits that are responsible for uncontrollable spasms, a characteristic of the disease. The researchers demonstrated that movement in mice with a Huntington's-like condition could be restored.

Su-Chun Zhang, a University of Wisconsin-Madison neuroscientist and the senior author of the study, said:

In the study Zhang, who is an expert in creating various types of brain cells from human embryonic or induce pluripotent stem cells, and his team focused on GABA neurons. The degradation of GABA cells causes the breakdown of a vital neural circuit and loss of motor function in individuals suffering from Huntington's disease.

According to Zhang, GABA neurons generate a vital neurotransmitter, a chemical that helps support the communication network in the brain that coordinates movement.

Zhang and his team at the UW-Madison Waisman Center, discovered how to generate large quantities of GABA neurons from human embryonic stem cells. The team's goal was to determine whether these cells would safely integrate into the brain of a mouse model of Huntington's disease.

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Huntington's Disease - Stem Cell Therapy Potential

Stem cell study ‘should aim at innovation in treatment’

By Bonnie James Deputy News Editor The stem cell and regenerative therapy programme, constituting a major part of research at Qatar Cardiovascular Research Centre (QCRC), has important clinical and scientific implications, co-chairman Prof Sir Magdi Yacoub has said. He was giving a keynote presentation at the Qatar International Conference on Stem Cell Science and Policy 2012, which concluded on Thursday at Qatar National Convention Centre. Myocardium (the muscular tissue of the heart) regeneration and tissue engineering and valves tissue engineering are among the focal areas at QCRC, which aims to establish in Qatar an internationally competitive centre of excellence for cardio-vascular research. QCRC, which has a heart muscle lab and a tissue engineering, regeneration lab, works with a mission to maintain a translational focus, relevant to the development of health policy and practice, and provide opportunities for capacity building, professional development and research collaborations in Qatar. It is also meant to provide opportunities for biotechnology development in Qatar and contribute to cardio-vascular health in the developing world through improved knowledge base, capacity building and development of appropriate tools and strategies focused on poorer countries. Cardio-vascular diseases (CVDs) kill 17mn people per year globally and there is particularly high incidence in the Middle East and Gulf region, Prof Yacoub pointed out. The incidence of CVDs is three times more in the region than in the UK, the US or Europe. Smoking, one of the main reasons for CVDs, is also increasing in the eastern Mediterranean region compared to the Americas. There is a significant lack of clinical, epidemiological and genetic data from this region and an overwhelming need exists to better understand epidemiology and disease mechanisms of CVDs. Research should then be linked to development of appropriate tools and strategies to strengthen prevention, diagnosis and treatment, he said. Pointing out that heart transplant options for those suffering from severe heart failure are becoming increasingly rare, Prof Yacoub observed that the number of donor hearts is going down globally. While we used to do up to 130 heart transplants a year at Royal Brompton and Harefield Hospitals in the UK in the late 80s, now we would be lucky to do 20, he said while emphasising the need to focus more on the reversibility of heart failure. Few recent drug trials have shown evidence of minor reverse remodelling and there have been near-complete reversal of almost every change in myocardium in some patients. There are unprecedented opportunities to unravel the secrets of heart failure at cellular and molecular levels, he stressed.

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Stem cell study ‘should aim at innovation in treatment’

A*STAR Scientists Make Groundbreaking Discovery on Stem Cell Regulation

Embryonic stem cells hold great potential for the development of cellular therapies, where stem cells are used to repair tissue damaged by disease or trauma. This is due to their unique ability to renew themselves and differentiate into any specific types of cell in the body. One of the challenges with cellular therapies is ensuring that ESCs are fully and efficiently differentiated into the correct cell type. This study sheds light on understanding how ESCs are regulated, which is essential to overcome these challenges and turn the vision of cell therapies into reality.

Using a mouse model, the team of scientists from IMB showed that high levels of Amd1 , a key enzyme in the polyamine synthesis pathway, is essential for maintenance of the ESC state and self renewal of ESCs. To further demonstrate the critical role of Amd1 in ESC self-renewal, the scientists showed that increasing Amd1 levels led to delayed ESC differentiation. The research also revealed that downregulation of Amd1 was necessary for differentiation of ESCs into neural precursor cells and that Amd1 is translationally regulated by a micro-RNA (miRNA), the first ever demonstration of miRNA-mediated regulation of the polyamine pathway.

While the polyamine pathway is well established and polyamines are known to be important in cancer and cell proliferation, their role in ESC regulation until now was unknown. This novel discovery, linking polyamine regulation to ESC biology, came about when the team set up a genome-wide screen to look for mRNAs under translational control in order to identify new regulators of ESC differentiation to neural precursor cells.

Dr Leah Vardy, Principle Investigator at the IMB and lead author of the paper, said, "The polyamines that Amd1 regulate have the potential to regulate many different aspects of self renewal and differentiation. The next step is to understand in more detail the molecular targets of these polyamines both in embryonic stem cells and cells differentiating to different cellular lineages. It is possible that manipulation of polyamine levels in embryonic stem cells through inhibitors or activators of the pathway could help direct the differentiation of embryonic stem cells to more clinically useful cell types."

Prof. Birgitte Lane, Executive Director of IMB, said, "This is a fine piece of fundamental research that will have breakthrough consequences in many areas and can bring about far-reaching applications. Developing cellular therapies is just one long-term clinical benefit of understanding ESC biology, which can also help develop stem cell systems for disease modeling, developing new drugs as well as a tool for researchers to answer other biological questions."

Notes for editors: The research findings can be found in the 1st March issue of Genes and Development under the title, "AMD1 is essential for ESC self-renewal and is translationally down-regulated on differentiation to neural precursor cells" by Dawei Zhang (1,4), Tianyun Zhao (1,4), Haw Siang Ang (2), Peini Chong (1), Ryotaro Saiki (3), Kazuei Igarashi (3), Henry Yang (2), and Leah A. Vardy (1,5).

1. Institute of Medical Biology, A*STAR, Singapore 2. Cancer Science Institute, National University of Singapore 3. Graduate School of Pharmaceutical Sciences, Chiba University, Japan 4. These authors contributed equally to this work 5. Corresponding author

About the Institute of Medical Biology (IMB)

IMB is one of the Biomedical Sciences Institutes of the Agency for Science, Technology and Research (A*STAR). It was formed in 2007, the 7th and youngest of the BMRC Research Institutes, with a mission to study mechanisms of human disease in order to discover new and effective therapeutic strategies for improved quality of life.

IMB hosts 20 research teams of international excellence in stem cells, genetic diseases, cancer and skin and epithelial biology, and works closely with clinical collaborators to target the challenging interface between basic science and clinical medicine. Its growing portfolio of strategic research topics is targeted at translational research on the mechanisms of human diseases, with a cell-to-tissue emphasis that can help identify new therapeutic strategies for disease amelioration, cure and eradication.

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A*STAR Scientists Make Groundbreaking Discovery on Stem Cell Regulation

Alzheimer's Stem Cell Research Patient Advocate Spotlight: The Faces of Neurodegenerative Disease – Video

(Part 3 of 7) Neal Hermanowicz, specialist, and, gave the keynote presentation at "Synapses Firing: Connections Made", a patient advocacy event hosted by the California stem cell funding agency (CIRM). The 100+ people in attendance heard from patient advocates about living with neurodegenerative disease and from scientists about recent progress in stem cell research that may lead to new treatments.

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Alzheimer's Stem Cell Research Patient Advocate Spotlight: The Faces of Neurodegenerative Disease - Video