The work has implications in two areas. In cancer treatment, it is desirable to inhibit cell proliferation. But to grow adult stem cells for transplantation to victims of injury or disease, it would be desirable to sustain proliferation until a sufficient number of cells have been produced to make a usable organ or tissue.

The study gives researchers a handle on how those two competing processes might be controlled. It was performed at the university's Hormel Institute in Austin, Minn., using mouse stem cells. The researchers, led by Hormel Institute Executive Director Zigang Dong and Associate Director Ann M. Bode, have published a report in the journal Nature: Structure and Molecular Biology.

"This is breakthrough research and provides the molecular basis for development of regenerative medicine," said Dong. "This research will aid in the development of the next generation of drugs that make repairs and regeneration within the body possible following damage by such factors as cancer, aging, heart disease, diabetes, or paralysis caused by traumatic injury."

The mechanism centers on a protein called Klf4, which is found in embryonic stem cells and whose activities include keeping those cells dividing and proliferating rather than differentiating. That is, Klf4 maintains the character of the stem cells; this process is called self-renewal. The researchers discovered that two enzymes, called ERK1 and ERK2, inactivate Klf; this allows the cells to begin differentiating into adult cells.

The two enzymes are part of a "bucket brigade" of signals that starts when a chemical messenger arrives from outside the embryonic stem cells. Chemical messages are passed to inside the cells, resulting in, among other things, the two enzymes swinging into action.

The researchers also discovered how the enzymes control Klf4. They attach a small molecule--phosphate, consisting of phosphorus and oxygen--to Klf4. This "tag" marks it for destruction by the cellular machinery that recycles proteins.

Further, they found that suppressing the activity of the two enzymes allows the stem cells to maintain their self-renewal and resist differentiation. Taken together, their findings paint a picture of the ERK1 and ERK2 enzymes as major players in deciding the future of embryonic stem cells--and potentially cancer cells, whose rapid growth mirrors the behavior of the stem cells.

Klf4 is one of several factors used to reprogram certain adult skin cells to become a form of stem cells called iPS (induced pluripotent stem) cells, which behave similarly to embryonic stem cells.

Also, many studies have shown that Klf4 can either activate or repress the functioning of genes and, in certain contexts, act as either an oncogene (that promotes cancer) or a tumor suppressor. Given these and their own findings reported here, the Hormel Institute researchers suggest that the self-renewal program of cancer cells might resemble that of embryonic stem cells.

"Although the functions of Klf4 in cancer are controversial, several reports suggest Klf4 is involved in human cancer development," Bode said.

Established in 1942, the Hormel Institute is a world-renowned medical research center specializing in research leading to cancer prevention and control. It is a research unit of the University of Minnesota and a collaborative cancer research partner with Mayo Clinic.

]]> Wed, 08 FEB 2012 08:47:16 AEST Atlanta GA (SPX) Dec 15, 2011 - The promise of stem cell research for drug discovery and cell-based therapies depends on the ability of scientists to acquire stem cell lines for their research. A survey of more than 200 human embryonic stem cell researchers in the United States found that nearly four in ten researchers have faced excessive delay in acquiring a human embryonic stem cell line and that more than one-quarter were unable to acquire a line they wanted to study.

"The survey results provide empirical data to support previously anecdotal concerns that delays in acquiring or an inability to acquire certain human embryonic stem cell lines may be hindering stem cell science in the United States," said Aaron Levine, an assistant professor in the School of Public Policy in the Ivan Allen College of Liberal Arts at the Georgia Institute of Technology.

Results of the survey were published in the December issue of the journal Nature Biotechnology. Funding for the study was provided by the Kauffman Foundation's Roadmap for an Entrepreneurial Economy Program.

Levine administered the web-based survey in November 2010 to more than 1,400 stem cell scientists working at U.S. academic and non-profit medical research institutions. Almost 400 respondents from 32 states completed the survey. Of those, 205 respondents reported using human embryonic stem cells in their research, and their responses were used in this study.

The surveyed scientists cited four main reasons for their problems accessing human embryonic stem cell lines: difficulty obtaining material transfer agreements, failure to acquire research approval from internal institutional oversight committees, cell line owners that were unwilling to share and federal policy considerations.

"Bureaucratic challenges may be inevitable in this ethically contentious and politically sensitive field, but policymakers should attempt to mitigate these issues by doing things like encouraging institutions to accept third-party ownership verification and providing clearer guidance on human embryonic stem cell research not eligible for federal funding," said Levine, who is also a member of the Georgia Tech Institute for Bioengineering and Bioscience.

The broad patents assigned to the initial inventors of the method used to isolate embryonic stem cells and numerous narrower patents claiming specific human embryonic stem cell-related techniques are also factors complicating access to human embryonic stem cell lines, according to Levine.

When survey respondents were asked how many of the more than 1,000 existing human embryonic stem cell lines they used, 76 percent reported using three or fewer lines and 54 percent reported using two or fewer lines in their research. More than half of the 130 respondents cited access issues as a major reason they chose to use specific cell lines in their research.

"These results illustrate that many human embryonic stem cell scientists in the United States are not conducting comparative studies with a diverse set of human embryonic stem cell lines, which raises concern that at least some results are cell-line specific rather than broadly applicable," said Levine.

"Federal and state funding agencies may want to consider encouraging research using multiple diverse human embryonic stem cell lines to improve the reliability of research results."

Embryonic stem cell lines are being used to develop new cellular therapies for various diseases, to screen for new drugs and to better understand inherited diseases. It's crucial that diverse lines are available for this research to ensure that all individuals benefit from the results.

While availability was cited as the most common factor affecting scientists' choices regarding which cell lines to use, other considerations included suitability for a specific project, familiarity with specific lines, a desire to reduce complications in the laboratory, cost, the extent of relevant literature and the preferences of scientists' colleagues.

Three of the initial human embryonic stem cell lines derived at the University of Wisconsin in the late 1990s were the lines most commonly used by respondents.

Cell lines H1, H9 and H7 were used by 79, 68 and 26 percent of respondents, respectively. Scientists also reported using more than 100 other lines, but each of these was used by fewer than 12 percent of respondents.

"Other research communities in the life sciences have experienced material access problems and they addressed them, in part, by creating centralized information and data sharing hubs, including public DNA sequence databases, tissue banks and mouse repositories. The stem cell research community has taken promising steps in this direction, but this analysis should encourage the community to continue and, if possible, accelerate these efforts," added Levine.

]]> Wed, 08 FEB 2012 08:47:16 AEST Washington DC (SPX) Dec 06, 2011 - Researchers have identified a new and relatively abundant pool of stem cells in the heart. The findings in the December issue of Cell Stem Cell, a Cell Press publication, show that these heart cells have the capacity for long-term expansion and can form a variety of cell types, including muscle, bone, neural and heart cells.

The researchers say the discovery may lay a foundation for much needed regenerative therapies aimed to enhance tissue repair in the heart. The damaged heart often doesn't repair itself well because of the incredibly hostile environment and wide-scale loss of cells, including stem cells, after a heart attack.

"In the end, we want to know how to preserve the stem cells that are there and to circumvent their loss," says Richard Harvey of the Victor Chang Cardiac Research Institute in Australia.

The newly described cardiac stem cells can be found in both developing and adult hearts, the evidence shows. As in the bone marrow and other organs, the colony-forming cells are found in the vicinity of blood vessels.

Harvey says despite the cells' ability to form those other cell types (a characteristic known as multipotency), he nevertheless suspects they have a bias toward heart tissue for a simple reason: "In an evolutionary sense, they've been dedicated to the heart for a long time." He suspects their flexibility is a byproduct of the need to remain responsive to the environment and to many types of injury.

The findings come at an important time, as stem cells harvested from human hearts during surgery are just beginning to show promise for reversing heart attack damage, Harvey noted.

"If we are serious about organ regeneration, we need to understand the biology," he says.

Igor Slukvin of the University of Wisconsin echoes that point in an accompanying commentary. "Understanding the developmental biology of the heart is instrumental in developing novel technologies for heart regeneration and cellular therapies," he writes. "It is critical to identify the type and origin of cells capable of reconstituting a heart."

While cell-based therapies do have potential for repairing damaged heart tissue, Harvey ultimately favors the notion of regenerative therapies designed to tap into the natural ability of the heart and other organs to repair themselves.

And there is more work to do to understand exactly what role these stem cells play in that repair process. His team is now exploring some of the factors that bring those cardiac stem cells out of their dormant state in response to injury and protect their "stemness."

Publishing in the Cell Stem Cell - December 2, 2011 print issue. Chong et al.: "Adult Cardiac-Resident MSC-like Stem Cells with a Proepicardial Origin."

]]> Wed, 08 FEB 2012 08:47:16 AEST Tokyo (AFP) Dec 3, 2011 - Scientists from Japan and Russia believe it may be possible to clone a mammoth after finding well-preserved bone marrow in a thigh bone recovered from permafrost soil in Siberia, a report said Saturday.

Teams from the Sakha Republic's mammoth museum and Japan's Kinki University will launch fully-fledged joint research next year aiming to recreate the giant mammal, Japan's Kyodo News reported from Yakutsk, Russia.

By replacing the nuclei of egg cells from an elephant with those taken from the mammoth's marrow cells, embryos with mammoth DNA can be produced, Kyodo said, citing the researchers.

The scientists will then plant the embryos into elephant wombs for delivery, as the two species are close relatives, the report said.

Securing nuclei with an undamaged gene is essential for the nucleus transplantation technique, it said.

For scientists involved in the research since the late 1990s, finding nuclei with undamaged mammoth genes has been a challenge. Mammoths became extinct about 10,000 years ago.

But the discovery in August of the well-preserved thigh bone in Siberia has increased the chances of a successful cloning.

Global warming has thawed ground in eastern Russia that is usually almost permanently frozen, leading to the discoveries of a number of frozen mammoths, the report said.

]]> Wed, 08 FEB 2012 08:47:16 AEST Los Angeles (UPI) Nov 29, 2011 - U.S. researchers say they've shown that blood stem cells can be engineered to create cancer-killing T-cells that seek out and attack a human melanoma.

Jerome Zack -- a scientist with the University of California, Los Angeles, Jonsson Comprehensive Cancer Center and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research -- said the tests, conducted on mice, prove blood stem cells can be genetically altered in a living organism to fight cancer.

"We knew from previous studies that we could generate engineered T-cells, but would they work to fight cancer in a relevant model of human disease, such as melanoma," Zack said Tuesday in a release.

In four of the nine mice studied, the antigen-expressing melanomas were eliminated. In the other five mice, the antigen-expressing melanomas decreased in size.

Researcher Dimitrios Vatakis said the approach turned a few engineered stem cells into an army of T-cells that responded to the presence of the melanoma antigen.

"These cells can exist in the periphery of the blood and if they detect the melanoma antigen, they can replicate to fight the cancer," he said.

The study appeared Monday in the early online edition of the Proceedings of the National Academy of Sciences.

]]> Wed, 08 FEB 2012 08:47:16 AEST Athens, GA (SPX) Nov 17, 2011 - In principle, stem cells offer scientists the opportunity to create specific cell types - such as nerve or heart cells - to replace tissues damaged by age or disease. In reality, coaxing stem cells to become the desired cell type can be challenging, to say the least.

In a paper published this week in the journal Proceedings of the National Academy of Sciences, however, scientists at the University of Georgia describe a method that - in a single step - directs undifferentiated, or pluripotent, stem cells to become neural crest cells, which are the precursors of bone cells, smooth muscle cells and neurons.

"Now that we have methods for efficiently making neural crest stem cells, we can start to use them to better understand human diseases," said lead author Stephen Dalton, Georgia Research Alliance Eminent Scholar of Molecular Biology and professor of cellular biology in the UGA Franklin College of Arts and Sciences.

"The cells can be also used in drug discovery and potentially in cell therapy, which involves the transplantation of cells."

The process by which a pluripotent stem cell, which has the ability to become any type of cell in the body, becomes a specific cell type is orchestrated by signaling molecules that activate specific "decision" pathways within cells.

As a stem cell divides, various combinations of these molecules at different points during its development narrow its possible outcomes so that it ultimately becomes one type of cell, a skin cell, for example, instead of, say, a muscle cell.

Until now, creating neural crest cells relied on a mix of science and serendipity. Scientists would take undifferentiated stem cells and direct them to become a related but different cell type known as neural progenitor cells.

The neural crest cells they really wanted would often show up as contaminants, which scientists would then isolate and use for their studies. Not surprisingly, the process was laborious, time consuming, expensive and sub-optimal for clinical applications.

The method developed by Dalton and a post-doctoral researcher in his laboratory, Laura Menendez, involves bathing cells in a solution of small molecules that suppress one pathway, known as Smad, and amplify another, known as Wnt.

The inhibition of Smad is used in the process that creates the related neural progenitor cells, which suggested that the pathway could also play a role in the development of neural crest cells.

Observing that the Wnt pathway is highly active in the formation of the neural crest in developing organisms led Dalton and his team to suspect that activating the pathway could give them the cells they needed.

After testing various concentrations of the signaling molecules and determining the optimal time to deliver them, the scientists discovered that they could create neural crest cells with little or no contamination of other cell types.

The new method cuts the amount of time required to generate the cells by approximately one-half. Dalton said another benefit is that instead of using costly large-molecule compounds known as growth factors and cytokines to direct the differentiation of cells, his method uses inexpensive small molecules that have a much higher degree of consistency.

With their newly developed ability to create neural crest cells, Dalton and his team are working to gain a deeper understanding of normal development - as well as what goes wrong in devastating diseases that are associated with neural crest defects, such as Hirschsprung's disease, DiGeorge syndrome and Treacher-Collins syndrome.

The cells that Dalton and his team have created are self-renewing, which means that multiple additional cells can be created from an initial batch. Having large numbers of cells that can easily be stored is essential for drug testing as well as for cell transplantation, the holy grail of stem cell science.

"Now that we've worked out ways for making the cells, we've greatly enhanced their potential in disease modeling and regenerative medicine," Dalton said.

Additional authors on the paper are Professor Parker Antin and Assistant Scientific Investigator Tatiana Yatskievych from the University of Arizona.

]]> Wed, 08 FEB 2012 08:47:16 AEST Luxembourg (AFP) Oct 18, 2011 - Europe's top court banned on Tuesday patents of stem cells when their extraction causes the destruction of a human embryo, a ruling that could have repercussions on medical research.

The European Union Court of Justice delved into the controversial issue after a German scientist was denied a patent on a method to create nerve cells from human embryonic stem cells.

Scientists warned that the ruling would damage stem cell research in Europe, while Catholic bishops hailed it as a victory for the protection of human life.

EU law, the court said, intended to "exclude any possibility of patentability where respect for human dignity could thereby be affected".

The Luxembourg-based judges were asked by the German Federal Court of Justice to provide an interpretation of a human embryo following an appeal from the scientist, Oliver Bruestle.

Bruestle, whose patent was challenged by Greenpeace, said there were already clinical applications for his invention to treat patients with Parkinson's disease.

"This unfortunate ruling wipes out years of transnational research by European researchers in one fell swoop," said Bruestle, a University of Bonn professor.

He warned that the work by European researchers will be to the benefit of scientists abroad, who will turn it into medical products that will eventually be imported back to Europe.

The EU court said the use of human embryos "for therapeutic or diagnostic purposes which are applied to the human embryo and are useful to it is patentable".

But, the judges added, "their use for purposes of scientific research is not patentable".

"A process which involves removal of a stem cell from a human embryo at the blastocyst stage, entailing the destruction of that embryo, cannot be patented."

Blastocyst is a later stage of embryonic development, almost five days after fertilisation.

The commission of the European bishops' conference, COMECE, welcomed the ruling "as a milestone in the protection of human life in EU legislation".

The bishops said attention must be given to scientific research on alternative sources such as adult stem cells or stem cells from umbilical cord blood.

"These methods enjoy wide acceptance both on scientific and ethical grounds," their statement said.

The court wrote that "the concept of 'human embryo' must be understood in a wide sense".

An egg must be considered a human embryo as soon as a sperm enters it "if that fertilisation is such as to commence the process of development of a human being", the court said.

But the judges added that even a non-fertilised egg can be considered a human embryo when the technique used to extract an embryo can trigger "the process of development of a human being".

]]> Wed, 08 FEB 2012 08:47:16 AEST London, UK (SPX) Oct 17, 2011 - This research, published on Oct. 12 on the Nature review website, provides evidence of a major concept could pave the way for the future use of these stem cells to treat humans, through perspective gene therapies.

For several years now, scientists have been able to produce cells with stem cell properties, by using specialized and mature cells from our body, such as skin cells.

These 'iPS' stem cells are said to be "pluripotent': they can provide specialized cells, upon demand, with the same gene pool as the original cells. iPS cells represent a potential basis for the exploration of several therapeutic areas, particularly transplants or gene therapy.

However, to date research conducted on these cells had not provided proof of their potential in vivo efficiency for the aforementioned types of use.

For the first time, researchers from the Sanger Institute and the University of Cambridge (United Kingdom), with collaboration from an Institut Pasteur/Inserm team in France, have demonstrated that the cells derived from iPS stem cells may be used within the framework of gene therapy to help counter pathological effects in a mice model with liver failure.

The researchers focussed on a rare genetic disease affecting the liver. It is caused by a point mutation in the a1-antitrypsin gene, which is essential for hepatic cells to function correctly.

Children display varying degrees of mild symptoms (jaundice, abdomen distension, etc.), but, in adulthood, these symptoms may progressively develop into a pulmonary emphysema and cirrhosis, where the only hope of a cure is a liver transplant.

Researchers from the University of Cambridge, directed by Ludovic Vallier and David Lomas, and from the Sanger Institute, coordinated by Allan Bradley, began by sampling patients' skin cells, which were then cultured in vitro for "differentiation" before applying the properties of the pluripotent stem cells: this is the "iPS cells" stage.

Through genetic engineering, scientists were then able to correct the mutation responsible for the disease. They then engaged the now "healthy" stem cells in the maturation process, leading them to differentiate to liver cells.

Scientists from the Institut Pasteur and Inserm, led by Helene Strick-Marchand in the mixed Institut Pasteur/Inserm Innate Immunity unit (directed by James Di Santo), then tested new human hepatic cells thus produced on an animal model afflicted with liver failure.

Their research showed that the cells were entirely functional and suited to integration in existing tissue and that they may contribute to liver regeneration in the mice treated.

This groundbreaking work, published in Nature, thus strengthened hopes in scientific and medical communities regarding the use of iPS cells to treat humans.

Targeted gene correction of a1-antitrypsin deficiency in induced pluripotent stem cells, Nature, en ligne le 12 octobre 2011. Kosuke Yusa (1)*, S. Tamir Rashid (2,3)*, Helene Strick-Marchand (4), Ignacio Varela (5), Pei-Qi Liu6, David E. Paschon (6), Elena Miranda (3,7), Adriana Ordonez (3), Nick Hannan (2), Foad Rouhani (1), Sylvie Darche (4), Graeme Alexander (3), Stefan J. Marciniak (3), Mamoru Hasegawa (8), Noemi Fusaki (8), Michael C. Holmes (6), James P. Di Santo (4), David A. Lomas (3), Allan Bradley (1) and Ludovic Vallier (2) */ Contributions egales des auteurs.

]]> Wed, 08 FEB 2012 08:47:16 AEST La Jolla CA (SPX) Oct 11, 2011 - Stem cells made by reprogramming patients' own cells might one day be used as therapies for a host of diseases, but scientists have feared that dangerous mutations within these cells might be caused by current reprogramming techniques. A sophisticated new analysis of stem cells' DNA finds that such fears may be unwarranted.

"We've shown that the standard reprogramming method can generate induced pluripotent stem cells that have very few DNA structural mutations, which are often linked to dangerous cell changes such as tumorigenesis," said Kristin Baldwin, associate professor at The Scripps Research Institute's Dorris Neuroscience Center and a senior author of the report, which appears in the October 7, 2011 issue of the journal Cell Stem Cell.

For this study the Baldwin lab collaborated with a genomics and bioinformatics expert, Ira M. Hall, an assistant professor of biochemistry and molecular genetics at the University of Virginia who is co-senior author.

The induced pluripotent stem cell (iPSC) technique was first described in 2006. It requires the insertion into an ordinary non-stem cell of four special genes, whose activities cause the cell to revert to a state like that of embryonic stem cell.

In principle, iPSCs may be used to repair diseased or damaged tissues, and because they are made from a patient's own cells, they shouldn't provoke an immune reaction.

But recent studies have found unacceptably high levels of mutations in iPSCs derived from adult human cells. That has led to widespread suspicion that the reprogramming process is largely to blame.

In the new study, the Scripps Research and University of Virginia researchers set out to investigate this issue using the latest chromosomal error-mapping methods.

"The techniques that our University of Virginia colleagues brought to this study are much more sensitive than anything else that's available right now," said Michael J. Boland, a research associate in the Scripps Research Baldwin lab and co-first author of the paper with Aaron R. Quinlan, a postdoctoral researcher in Hall's lab.

The new methods included a high-resolution version of a DNA-error-finding technique known as paired-end mapping, and an advanced algorithm, "HYDRA," for handling the voluminous mapping data.

To generate the iPSCs, the Scripps Research team followed the standard, four-gene reprogramming procedure, but sought to minimize other potential sources of DNA mutations that might have influenced some previously reported results.

The donor cells they selected were not decades-old human skin cells, but relatively error-free fibroblast cells from fetal mice. The researchers also kept these fibroblast cells only briefly in lab dishes before reprogramming them.

When the team members analyzed these iPSCs they used two strategies to distinguish which mutations were present in rare donor fibroblast cells and which were newly acquired during reprogramming. Their advanced techniques also allowed them to find more kinds of mutations, across a wider range of the genome, than ever before.

Yet instead of finding more mutations, they found almost none. "We sequenced three iPSC lines at very high resolution, and were surprised to find that very few changes to the chromosomal sequence had appeared during reprogramming," said Boland.

Each of the iPSC lines contained only a single mutation that probably originated from the reprogramming process; two affected genes while the other appeared not to. Mutations inherited from the donor fibroblast cell were present in one pair of lines, while a second line "inherited" none.

The researchers were particularly cheered by the complete absence of new "retroelement transpositions"-mutations caused by retrovirus-like sequences that burrowed into the mammalian genome long ago that can become active again in certain cell types.

All cells have ways to suppress these retroelements, but the suppression mechanisms in normal cells are different from those in stem cells, so the researchers had worried that retroelements would be allowed to escape suppression during the transition to a stem cell state.

While no previous surveys of iPSCs could detect these mutations, this study showed that despite very sensitive detection of controls, no retroelements had become active during reprogramming. "That was is very encouraging, because retroelement mutations can be very damaging to the genome," Boland said.

Some of the mutations seen in human iPSCs in previous studies might have been due to incomplete reprogramming that impaired the cells' DNA-maintenance mechanisms.

In this study using mouse iPSCs, however, there was no doubt that a complete reprogramming to an embryonic state had occurred: all three iPSC lines were used to produce live, fertile mice, in work that Boland, Baldwin, and their colleagues described in Nature in 2009.

"The mice generated from these cells have survived to a normal lab-mouse lifespan without obvious diseases that might arise from new DNA mutations," said Baldwin.

Her lab now is trying to determine whether a reprogramming method similar to the one used with mouse iPSCs in this study could also yield relatively error-free human iPSCs.

"If our results with these mouse cells are applicable to human cells, then selecting better donor cells and using more sensitive genome-survey techniques should allow us to identify reprogramming methods that can produce human iPSCs that will be safer or more useful for therapies than current lines," she said.

Other contributors to the paper, "Genome Sequencing of Mouse Induced Pluripotent Stem Cells Reveals Retroelement Stability and Infrequent DNA Rearrangement during Reprogramming," are Mitchell L. Leibowitz and Svetlana Shumilina of Hall's lab at the University of Virginia, and Sidney M. Pehrson of Baldwin's lab at Scripps Research.

]]> Wed, 08 FEB 2012 08:47:16 AEST Atlanta GA (SPX) Sep 21, 2011 - Researchers have shown they can reverse the aging process for human adult stem cells, which are responsible for helping old or damaged tissues regenerate. The findings could lead to medical treatments that may repair a host of ailments that occur because of tissue damage as people age.

A research group led by the Buck Institute for Research on Aging and the Georgia Institute of Technology conducted the study in cell culture, which appears in the September 1, 2011 edition of the journal Cell Cycle

The regenerative power of tissues and organs declines as we age. The modern day stem cell hypothesis of aging suggests that living organisms are as old as are its tissue specific or adult stem cells. Therefore, an understanding of the molecules and processes that enable human adult stem cells to initiate self-renewal and to divide, proliferate and then differentiate in order to rejuvenate damaged tissue might be the key to regenerative medicine and an eventual cure for many age-related diseases.

A research group led by the Buck Institute for Research on Aging in collaboration with the Georgia Institute of Technology, conducted the study that pinpoints what is going wrong with the biological clock underlying the limited division of human adult stem cells as they age.

"We demonstrated that we were able to reverse the process of aging for human adult stem cells by intervening with the activity of non-protein coding RNAs originated from genomic regions once dismissed as non-functional 'genomic junk'," said Victoria Lunyak, associate professor at the Buck Institute for Research on Aging.

Adult stem cells are important because they help keep human tissues healthy by replacing cells that have gotten old or damaged. They're also multipotent, which means that an adult stem cell can grow and replace any number of body cells in the tissue or organ they belong to.

However, just as the cells in the liver, or any other organ, can get damaged over time, adult stem cells undergo age-related damage. And when this happens, the body can't replace damaged tissue as well as it once could, leading to a host of diseases and conditions.

But if scientists can find a way to keep these adult stem cells young, they could possibly use these cells to repair damaged heart tissue after a heart attack; heal wounds; correct metabolic syndromes; produce insulin for patients with type 1 diabetes; cure arthritis and osteoporosis and regenerate bone.

The team began by hypothesizing that DNA damage in the genome of adult stem cells would look very different from age-related damage occurring in regular body cells. They thought so because body cells are known to experience a shortening of the caps found at the ends of chromosomes, known as telomeres.

But adult stem cells are known to maintain their telomeres. Much of the damage in aging is widely thought to be a result of losing telomeres. So there must be different mechanisms at play that are key to explaining how aging occurs in these adult stem cells, they thought.

Researchers used adult stem cells from humans and combined experimental techniques with computational approaches to study the changes in the genome associated with aging.

They compared freshly isolated human adult stem cells from young individuals, which can self-renew, to cells from the same individuals that were subjected to prolonged passaging in culture. This accelerated model of adult stem cell aging exhausts the regenerative capacity of the adult stem cells. Researchers looked at the changes in genomic sites that accumulate DNA damage in both groups.

"We found the majority of DNA damage and associated chromatin changes that occurred with adult stem cell aging were due to parts of the genome known as retrotransposons," said King Jordan, associate professor in the School of Biology at Georgia Tech.

"Retroransposons were previously thought to be non-functional and were even labeled as 'junk DNA', but accumulating evidence indicates these elements play an important role in genome regulation," he added.

While the young adult stem cells were able to suppress transcriptional activity of these genomic elements and deal with the damage to the DNA, older adult stem cells were not able to scavenge this transcription. New discovery suggests that this event is deleterious for the regenerative ability of stem cells and triggers a process known as cellular senescence.

"By suppressing the accumulation of toxic transcripts from retrotransposons, we were able to reverse the process of human adult stem cell aging in culture," said Lunyak.

"Furthermore, by rewinding the cellular clock in this way, we were not only able to rejuvenate 'aged' human stem cells, but to our surprise we were able to reset them to an earlier developmental stage, by up-regulating the "pluripotency factors" - the proteins that are critically involved in the self-renewal of undifferentiated embryonic stem cells." she said.

Next the team plans to use further analysis to validate the extent to which the rejuvenated stem cells may be suitable for clinical tissue regenerative applications.

The study was conducted by a team with members from the Buck Institute for Research on Aging, the Georgia Institute of Technology, the University of California, San Diego, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, International Computer Science Institute, Applied Biosystems and Tel-Aviv University. Inhibition of activated pericentromeric SINE/Alu repeat transcription in senescent human adult stem cells reinstates self-renewal. Cell Cycle, Volume 10, Issue 17, September 1, 2011.

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