Synthetic protein amplifies genes needed for stem cells

Public release date: 16-Feb-2012
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Contact: Tara Womersley
tara.womersley@ed.ac.uk
44-131-650-9836
University of Edinburgh

Scientists have found a way to generate and maintain stem cells much more efficiently by amplifying the effect of an essential protein.

Researchers from Denmark, Scotland and the USA have created synthetic versions of a protein, which manipulates adult cells ? such as skin cells ? so that they can subsequently revert to an earlier, embryonic like state. These reverted cells have the potential to become any cell in the body.

As well as reverting adult cells to this state ? known as induced pluripotent stem cells , the protein also plays a key role in maintaining embryonic stem cells in a pure form. If the protein ? Oct4 ? is not present, the embryonic stem cells will start to differentiate into specific cells.

In order to reprogamme adult cells to have stem cell properties viruses need to be added to cell cultures to trigger production of significant quantities of Oct4.

Oct4 plays a powerful role in regulating stem cell genes. However, while large quantities of Oct4 are needed too much of it can ruin the properties of stem cells.

Scientists, whose work is published in the journal Cell Reports, were able to overcome this by producing a synthetic version of Oct4 that amplified the effect of the protein in its natural form.

The synthetic version of Oct4 was much more efficient in turning on genes that instruct cells on how to be stem cells and, as a result, the cells did not need as much Oct4 for either reprogramming or to remain as stem cells ? thereby eliminating problems caused by too much Oct4.

In fact, the synthetic Oct4 could support stem cells under conditions that they do not normally grow. These findings could also help scientists find new ways generate stem cells in the laboratory.

The study showed that Oct4 was mainly responsible for turning on genes that instruct cells on how to become stem cells, rather than turning off genes that encourage the cells to differentiate.

"Our discovery is an important step towards generating and maintaining stem cells much more effectively," says Professor Joshua Brickman, affiliated with both The Danish Stem Cell Center (DanStem), University of Copenhagen and Medical Research Council Centre for Regenerative Medicine at the University of Edinburgh.

"Embryonic stem cells are characterized, among other things, by their ability to perpetuate themselves indefinitely and differentiate into all the cell types in the body ? a trait called pluripotency. But to be able to use them medically, we need to be able to maintain them in a pure state, until they're needed. When we want to turn a stem cell into a specific cell, such as insulin producing beta cell, or a nerve cell in the brain, we'd like this process to occur accurately and efficiently. This will not be possible if we don't understand how to maintain stem cells as stem cells. As well as maintaining embryonic stem cells in their pure state more effectively, the artificially created Oct4 was also more effective at reprogramming adult cells into so-called induced Pluripotent Stem cells, which have many of the same traits and characteristics as embryonic stem cells but can derived from the patients to both help study degenerative disease and eventually treat them.."

Oct4 is a so-called transcription factor ? a protein that binds to specific DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to mRNA. The synthetic version of Oct4 was created by using recombinant DNA technology whereby a gene was modified to produce new and more active protein. The modified gene was either introduced into stem cells or used to reprogram adult skin cells.

If scientists can exploit this programming of stem cell programs, it will improve the ability to generate stem cells directly from a patient. These cells could in turn potentially be used for individualised studies and for developing individualized therapies for degenerative diseases such as type 1 diabetes and neuro-degenerative diseases.

###

The paper "Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency", is published in Cell Reports on February 16, 2012, 12:00 EST US time/18:00 Danish time/17:00 UK time. The study involved mouse embryonic stem cells, early embryonic progenitors cells in frogs as well as iPS cells from both mouse and human sources. The research was supported by grants from the Novo Nordisk Foundation (DK), the Medical Reseach Council and the Biotechnology and Biological Sciences Research Council (MRC and BBSRC, UK).

Contact: Tara Womersley, Press and PR Officer, University of Edinburgh, 44-131-650-9836 or 44-7791-355-804

Link to Cell Report: http://cellreports.cell.com/

Embargo: Until February 16 at 12:00 EST US time/18:00 Danish time/17:00 UK time

About DanStem

The Danish Stem Cell Center opened in the Summer 2011 as a hub for international basic, translational and early clinical stem cell research. Professor Brickman and his group joined DanStem in October 2011 to partake in the build-up the center.

DanStem address basic questions in stem cell and developmental biology, and develop novel stem cell based therapeutic approaches for diabetes and cancer. It is supported by two major grants from Novo Nordisk Foundation (DKK 350 million (? 47 million)) and the Danish Research Council for Strategic Research (DKK 64.8 million (? 8,7 million)), respectively. More information about DanStem at: http://danstem.ku.dk

About Medical Research Council Centre for Regenerative Medicine

The MRC Centre for Regenerative Medicine (CRM) is a world leading research centre based at the University of Edinburgh. Together we study stem cells, disease and tissue repair to advance human health. Our research is aimed at developing new treatments for major diseases including cancer, heart disease, diabetes, degenerative diseases such as multiple sclerosis and Parkinson's disease, and liver failure. http://www.crm.ed.ac.uk

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Synthetic protein amplifies genes needed for stem cells

Area woman’s disease puts focus on need for stem cell donations

Posted: Thursday, February 16, 2012 8:05 am | Updated: 2:27 pm, Thu Feb 16, 2012.

PITTSBURG — A brief cheek swab can wind up saving a life — and the life saved may be one of East Texas’ own.

Be The Match Registry will be camped out in the atrium of East Texas Medical Center in Pittsburg from 10 a.m. to 2 p.m. on Feb. 23 to take samples for the registry, which is just a sweep of the inside of a person’s cheek with a cotton swab. The organization nationally matches stem cell donors with those in need of a transplant.

Pittsburg resident Wanda Warrick has been diagnosed with Myelodysplastic Syndrome, a precursor to leukemia, and is in need of a stem cell transplant. She and her husband, Larry Warrick, joined up with Be The Match to help search for a donor.

He said the other way of looking at it would be if they wait too long, the disease could go further south and turn into leukemia, which is a cancer of the bone marrow.

Wanda Warrick was diagnosed five-and-a-half years ago with the disease and was told that within four or five years she would have to have a stem cell transplant. Larry Warrick said they’ve been lucky with the disease so far.

“Hers has been real slow to decline,” he said.

The couple went to visit a specialist in Seattle, where doctors started researching it before anyone else, he said.

“They do about 600 transplants a year,” Larry said. “(The doctor) goes, ‘10 years at the most, anybody would go with that. You’re one of the more fortunate ones.’ ”

Wanda Warrick is a former LVN, but Larry Warrick said the disease has taken that away from her, since one of the symptoms is a lessening of the body’s immune responses.

“She has a low platelet count,” he said. “If she’s cut, she bleeds easily. She gets sick easily. It took her out of the nursing field because she couldn’t make it through a full day’s shift.”

Now, Larry said, she can do some light housework in the morning, but fades around noon and has to nap.

The donor part of the transplant procedure is, thanks to recent technology, fairly simple — and free, thanks to Be The Match and the Warricks’ insurance. After the cheek swab, the donor is put on the list and checked against those in need of a transplant. After a hormone injection every day for five days, the donor is attached to a machine like a kidney dialysis machine, which circulates the blood through the machine, draws out the stem cells and then sends the blood back into the body through a needle in the other arm.

“Every once in a while, if they can’t get enough, they will do a bone marrow transplant,” Larry Warrick said. “Used to they had to do it from the bone marrow all the time.”

Wanda’s part of the transplant is harder. In order for her body to receive the new stem cells, the doctors have to kill off as much of her original bone marrow as possible. This is done through chemotherapy and radiation.

“There’s a 35 percent chance this could kill her,” Larry Warrick said. “It’s one of the most difficult decisions a person can make.”

By killing off all of the bone marrow, the body is defenseless against any disease, even the common cold, which could be fatal.

The new stem cells would then be injected into Wanda Warrick and allowed to take over her bone marrow. She would then be put on transplant medication anywhere from a few months to several years to the rest of her life, depending on how close the match is and how successful the transplant.

His wife has decided to go through with the surgery, he said, if a match can be found.

“She’s going to have it done in Dallas,” Larry Warrick said. “She’s going to wait until after next May so she can see at least one of her grandchildren graduate.”

He encourages everyone to come donate.

“They might be able to save someone’s life, maybe not Wanda’s, but someone’s, and that would make her happy,” he said.

Not a lot of people are aware of this, he said, but bone marrow or stem cell donation is racially specific.

“Whites donate for whites, Indians for Indians, Hispanics for Hispanics,” Warrick said. “There is a greater need for black, Hispanic and oriental, because they donate less than white people. That’s a need a lot of people don’t realize.”

He said he’s grateful that ETMC is letting Be The Match use their facility for the drive.

“I’d like to thank ETMC,” he said.

For those who cannot make the first registration drive, another registration will be held March 31 also at ETMC Pittsburg and will include Carter BloodCare taking blood donations as well.

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Area woman’s disease puts focus on need for stem cell donations

Bioheart to Present at BioFlorida's Saturday Exchange

SUNRISE, Fla., Feb. 15, 2012 (GLOBE NEWSWIRE) -- Bioheart (BHRT.OB), a leader in developing stem cell therapies to treat cardiovascular diseases, today announced that they have been chosen as a presenter in the BioFlorida Saturday Exchange conference later this month.

The Saturday Exchange is a reprise of the successful Biomed Exchange meeting, held for many years during the 1980-90's. Well over 100 life science professionals gathered in Miami on a Saturday morning each month to learn about various aspects of the community's growing life sciences cluster. The Exchange will take place at University of Miami's Life Science & Technology Park.

The Keynote Speaker is Bioheart's Chairman William P. Murphy Jr., MD. Dr. Murphy will share his career experiences and insights as a leading entrepreneur in the medical device industry, spanning the founding of Cordis Corporation to more recent ventures. In addition, Mike Tomas, Bioheart's president and CEO and Kristin Comella, Bioheart's CSO will present the use of stem cells in degenerative diseases

"The Saturday Exchange brings together many professionals to discuss the field of biotechnology," said Mike Tomas. "Bioheart is excited about the opportunity to represent the South Florida community and share our experiences in the field of regenerative medicine."

About Bioheart

Bioheart (BHRT.OB) is committed to developing stem cell therapies to treat congestive heart failure, lower limb ischemia, chronic heart ischemia, acute myocardial infarctions and other medical problems. The company focuses on the discovery and development of therapies that will improve patients' quality of life and reduce health care costs and hospitalizations. Bioheart's leading product, MyoCell, is a muscle-derived cell therapy designed to populate regions of scar tissue within a patient's heart to improve cardiac function.

For more information on Bioheart, visit http://www.bioheartinc.com.

Forward-Looking Statements: Except for historical matters contained herein, statements made in this press release are forward-looking statements. Without limiting the generality of the foregoing, words such as "may," "will," "to," "plan," "expect," "believe," "anticipate," "intend," "could," "would," "estimate," or "continue" or the negative other variations thereof or comparable terminology are intended to identify forward-looking statements.

Forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Also, forward-looking statements represent our management's beliefs and assumptions only as of the date hereof. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future.

The Company is subject to the risks and uncertainties described in its filings with the Securities and Exchange Commission, including the section entitled "Risk Factors" in its Annual Report on Form 10-K for the year ended December 31, 2010, and its Quarterly Report on Form 10-Q for the quarter ended September 30, 2011.

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Bioheart to Present at BioFlorida's Saturday Exchange

U-M Human Embryonic Stem Cell Line Placed On National Registry for Researchers

Line is first from U-M accepted to the U.S. National Institutes of Health registry, now available for federally-funded research

ANN ARBOR, Mich., Feb. 14, 2012 /PRNewswire-USNewswire/ -- The University of Michigan's first human embryonic stem cell line will be placed on the U.S. National Institutes of Health's registry, making the cells available for federally-funded research. It is the first of the stem cell lines derived at the University of Michigan to be placed on the registry.

The line, known as UM4-6, is a genetically normal line, derived in October 2010 from a cluster of about 30 cells removed from a donated five-day-old embryo roughly the size of the period at the end of this sentence. That embryo was created for reproduction but was no longer needed for that purpose and was therefore about to be discarded.

"This is significant, because acceptance of these cells on the registry demonstrates our attention to details of proper oversight, consenting, and following of NIH guidelines established in 2009," says Gary Smith, Ph.D., who derived the line and also is co-director of the U-M Consortium for Stem Cell Therapies, part of the A. Alfred Taubman Medical Research Institute.

"It now makes the line available to researchers who can apply for federal funding to use it in their work; this is an important step."

The line is the culmination of years of planning and preparation and was made possible by Michigan voters' November 2008 approval of a state constitutional amendment permitting scientists here to derive embryonic stem cell lines using surplus embryos from fertility clinics or embryos with genetic abnormalities and not suitable for implantation.

"We expect these cells will be used by investigators worldwide to enhance our understanding of stem cell biology, and together with disease-specific lines, discover treatments and cures for genetic diseases," says Smith, who is a professor in the Department of Obstetrics and Gynecology at the University of Michigan Medical School.

U-M is among just a handful of U.S. universities creating human embryonic stem cell lines. There are only 147 stem cell lines available on the registry.

"We envision in the future that investigators will be able to use the genetically normal embryonic stem cell lines like UM4-6, together with disease-specific embryonic stem cell lines, as a model system to investigate what causes these diseases and come up with treatments," says Sue O'Shea, professor of Cell and Developmental Biology, and co-director of the Consortium for Stem Cell Therapies.

U-M also has two other human embryonic stem cells lines submitted to the national registry. Both are disease specific, the first carrying the genetic defect that causes hemophilia B, and the other carries the gene responsible for Charcot-Marie-Tooth disease, a hereditary neurological disorder.

Smith expects to soon submit eight additional human embryonic stem lines for consideration on the national registry: three genetically normal and five new disease specific lines.

This is a historic achievement that will lead to treatments and cures for serious, life-altering diseases and is more evidence that our University of Michigan researchers are leading the world in cutting-edge science that will impact health around the globe, says Eva Feldman, M.D., Ph.D., director of the A. Alfred Taubman Medical Research Institute.

"This is another major step forward for medical science in Michigan. This opens us another avenue for researchers to really begin exploring the causes and progression of those diseases, with the ultimate goal of finding new therapies for patients," says Feldman.

Contributors to the A. Alfred Taubman Medical Research Institute's Consortium for Stem Cell Therapies include the Taubman Institute; the Office of the Executive Vice President for Medical Affairs; the Office of the Medical School Dean; the Comprehensive Cancer Center; the Department of Pediatrics and Communicable Diseases; the Office of the Vice President for Research; the School of Dentistry; the Department of Pathology; the Department of Cell and Developmental Biology; the College of Engineering; the Life Sciences Institute; the Department of Neurology; and U-M's Michigan Institute for Clinical and Health Research.

A. Alfred Taubman, founder and chair of U-M's Taubman Institute, called the registry placement a tremendous step for stem cell research.

"I consider stem cells to be a modern medical miracle – the most exciting advance in medicine since antibiotics. The progress we have made throughout the state in stem cell research has been nothing short of remarkable," says Taubman.

"This milestone means much to the University of Michigan and the state of Michigan, but also to the world. It offers another route for researchers to move ahead in studying these horrible diseases. We hope it is the first of many lines that the University of Michigan can contribute to the global efforts to improve human health."

For more information about the A. Alfred Taubman Medical Research Institute at the University of Michigan Medical School, visit http://www.taubmaninstitute.org

For more information about stem cell research at U-M, visit http://www.umich.edu/stemcell

SOURCE University of Michigan Health System

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U-M Human Embryonic Stem Cell Line Placed On National Registry for Researchers

UM Human Embryonic Stem Cell Line Placed On National Registry

ANN ARBOR — The University of Michigan’s first human embryonic stem cell line will be placed on the U.S. National Institutes of Health’s registry, making the cells available for federally funded research. It is the first of the stem cell lines derived at the University of Michigan to be placed on the registry.

The line, known as UM4-6, is a genetically normal line, derived in October 2010 from a cluster of about 30 cells removed from a donated five-day-old embryo roughly the size of the period at the end of this sentence. That embryo was created for reproduction through in-vitro fertilization but was no longer needed for that purpose and was therefore about to be discarded.

“This is significant, because acceptance of these cells on the registry demonstrates our attention to details of proper oversight, consenting, and following of NIH guidelines established in 2009,” says Gary Smith, who derived the line and also is co-director of the U-M Consortium for Stem Cell Therapies, part of the A. Alfred Taubman Medical Research Institute. “It now makes the line available to researchers who can apply for federal funding to use it in their work; this is an important step.”

The line is the culmination of years of planning and preparation and was made possible by Michigan voters’ November 2008 approval of a state constitutional amendment permitting scientists here to derive embryonic stem cell lines using surplus embryos from fertility clinics or embryos with genetic abnormalities and not suitable for implantation.

“We expect these cells will be used by investigators worldwide to enhance our understanding of stem cell biology, and together with disease-specific lines, discover treatments and cures for genetic diseases,” says Smith, who is a professor in the Department of Obstetrics and Gynecology at the University of Michigan Medical School.

UM is among just a handful of United States universities creating human embryonic stem cell lines. There are only 147 stem cell lines available on the registry.

“We envision in the future that investigators will be able to use the genetically normal embryonic stem cell lines like UM4-6, together with disease-specific embryonic stem cell lines, as a model system to investigate what causes these diseases and come up with treatments,” said Sue O’Shea, professor of Cell and Developmental Biology, and co-director of the Consortium for Stem Cell Therapies.

UM also has two other human embryonic stem cells lines submitted to the national registry. Both are disease specific, the first carrying the genetic defect that causes hemophilia B, and the other carries the gene responsible for Charcot-Marie-Tooth disease, a hereditary neurological disorder.

Smith expects to soon submit eight additional human embryonic stem lines for consideration on the national registry: three genetically normal and five new disease specific lines.

This is a historic achievement that will lead to treatments and cures for serious, life-altering diseases and is more evidence that our University of Michigan researchers are leading the world in cutting-edge science that will impact health around the globe, says Eva Feldman, M.D., director of the A. Alfred Taubman Medical Research Institute.

“This is another major step forward for medical science in Michigan,” Feldman said. “This opens us another avenue for researchers to really begin exploring the causes and progression of those diseases, with the ultimate goal of finding new therapies for patients.”

Contributors to the A. Alfred Taubman Medical Research Institute’s Consortium for Stem Cell Therapies include the Taubman Institute; the Office of the Executive Vice President for Medical Affairs; the Office of the Medical School Dean; the Comprehensive Cancer Center; the Department of Pediatrics and Communicable Diseases; the Office of the Vice President for Research; the School of Dentistry; the Department of Pathology; the Department of Cell and Developmental Biology; the College of Engineering; the Life Sciences Institute; the Department of Neurology; and U-M’s Michigan Institute for Clinical and Health Research.

A. Alfred Taubman, founder and chair of UM’s Taubman Institute, called the registry placement a tremendous step for stem cell research.

“I consider stem cells to be a modern medical miracle – the most exciting advance in medicine since antibiotics. The progress we have made throughout the state in stem cell research has been nothing short of remarkable,” Taubman said. “This milestone means much to the University of Michigan and the state of Michigan, but also to the world. It offers another route for researchers to move ahead in studying these horrible diseases. We hope it is the first of many lines that the University of Michigan can contribute to the global efforts to improve human health.”

For more information about the A. Alfred Taubman Medical Research Institute at the University of Michigan Medical School, visit http://www.taubmaninstitute.org

The rest is here:
UM Human Embryonic Stem Cell Line Placed On National Registry

U-M human embryonic stem cell line placed on national registry

The line, known as UM4-6, is a genetically normal line, derived in October 2010 from a cluster of about 30 cells removed from a donated five-day-old embryo roughly the size of the period at the end of this sentence. That embryo was created for reproduction but was no longer needed for that purpose and was therefore about to be discarded.

"This is significant, because acceptance of these cells on the registry demonstrates our attention to details of proper oversight, consenting, and following of NIH guidelines established in 2009," says Gary Smith, Ph.D., who derived the line and also is co-director of the U-M Consortium for Stem Cell Therapies, part of the A. Alfred Taubman Medical Research Institute.

This video is not supported by your browser at this time.

"It now makes the line available to researchers who can apply for federal funding to use it in their work; this is an important step."

The line is the culmination of years of planning and preparation and was made possible by Michigan voters' November 2008 approval of a state constitutional amendment permitting scientists here to derive embryonic stem cell lines using surplus embryos from fertility clinics or embryos with genetic abnormalities and not suitable for implantation.

"We expect these cells will be used by investigators worldwide to enhance our understanding of stem cell biology, and together with disease-specific lines, discover treatments and cures for genetic diseases," says Smith, who is a professor in the Department of Obstetrics and Gynecology at the University of Michigan Medical School.

U-M is among just a handful of U.S. universities creating human embryonic stem cell lines. There are only 147 stem cell lines available on the registry.

"We envision in the future that investigators will be able to use the genetically normal embryonic stem cell lines like UM4-6, together with disease-specific embryonic stem cell lines, as a model system to investigate what causes these diseases and come up with treatments," says Sue O'Shea, professor of Cell and Developmental Biology, and co-director of the Consortium for Stem Cell Therapies.

U-M also has two other human embryonic stem cells lines submitted to the national registry. Both are disease specific, the first carrying the genetic defect that causes hemophilia B, and the other carries the gene responsible for Charcot-Marie-Tooth disease, a hereditary neurological disorder.

Smith expects to soon submit eight additional human embryonic stem lines for consideration on the national registry: three genetically normal and five new disease specific lines.

This is a historic achievement that will lead to treatments and cures for serious, life-altering diseases and is more evidence that our University of Michigan researchers are leading the world in cutting-edge science that will impact health around the globe, says Eva Feldman, M.D., Ph.D., director of the A. Alfred Taubman Medical Research Institute.

"This is another major step forward for medical science in Michigan. This opens us another avenue for researchers to really begin exploring the causes and progression of those diseases, with the ultimate goal of finding new therapies for patients," says Feldman.

Contributors to the A. Alfred Taubman Medical Research Institute's Consortium for Stem Cell Therapies include the Taubman Institute; the Office of the Executive Vice President for Medical Affairs; the Office of the Medical School Dean; the Comprehensive Cancer Center; the Department of Pediatrics and Communicable Diseases; the Office of the Vice President for Research; the School of Dentistry; the Department of Pathology; the Department of Cell and Developmental Biology; the College of Engineering; the Life Sciences Institute; the Department of Neurology; and U-M's Michigan Institute for Clinical and Health Research.

A. Alfred Taubman, founder and chair of U-M's Taubman Institute, called the registry placement a tremendous step for stem cell research.

"I consider stem cells to be a modern medical miracle – the most exciting advance in medicine since antibiotics. The progress we have made throughout the state in stem cell research has been nothing short of remarkable," says Taubman.

"This milestone means much to the University of Michigan and the state of Michigan, but also to the world. It offers another route for researchers to move ahead in studying these horrible diseases. We hope it is the first of many lines that the University of Michigan can contribute to the global efforts to improve human health."

Provided by University of Michigan Health System (news : web)

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U-M human embryonic stem cell line placed on national registry

Young stem cells make rapidly aging mice live longer and healthier – Video

17-01-2012 13:20 Researchers from the University of Pittsburgh School of Medicine found that a shot of young stem cells made rapidly aging mice live longer and healthier. Johnny Huard, Ph.D., professor in the Departments of Orthopaedic Surgery and of Microbiology and Molecular Genetics, Pitt School of Medicine, and director of the Stem Cell Research Center at Pitt and Children's Hospital of Pittsburgh of UPMC, and Laura Niedernhofer, MD, Ph.D., associate professor in the University of Pittsburgh's Department of Microbiology and Molecular Genetics and the University of Pittsburgh Cancer Institute (UPCI), discuss their research findings, which were published in the Jan. 3 edition of Nature Communications.

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Young stem cells make rapidly aging mice live longer and healthier - Video

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19-01-2012 09:27 Dr. Irv Weissman of CIRM (California Institute of Regenerative Medicine) explain the difference between adult and embryonic stem cells, how they are used and their potential.

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Integra Medical Center 4 Dec 2010.MOV – Video

04-02-2011 17:01 I have been looking for a cure to my situation for some time now. On Dec 4th of 2010 I traveled to the lower part of Texas and went across the border to a place called Integra Medical Center to see a man by the name of Dr. Omar Gonzalez. There I received 5 placenta stem cell implants. This video was so I could track my progress.

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