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Life Technologies and Cellular Dynamics International Partner for Global Commercialization of Novel Stem Cell …

Posted: June 13, 2012 at 6:12 am

CARLSBAD, Calif., June 12, 2012 /PRNewswire/ -- Life Technologies Corporation (LIFE) today announced a partnership with Cellular Dynamics International (CDI), the world's largest producer of human cells derived from induced pluripotent stem (iPS) cells, to commercialize a set of three new products optimized to consistently develop and grow human iPS cells for both research and bioproduction.

The partnership marries CDI's leadership in human iPS cell development with Life Technologies' expertise in stem cell research tool manufacturing and global distribution network to make these novel technologies accessible to researchers around the world. Life Technologies' commercialization of Essential 8 Medium, Vitronectin (VTN-N), and Episomal iPSC Reprogramming Vectors addresses several challenges associated with developing relevant cells for use in a wide range of studies, from basic and translational research to drug discovery efforts. The effectiveness of these products is the focus of recent validation studies published in the journals Nature Methods and PLoS One.

"The launch of these new stem cell culture products furthers CDI founder and stem cell pioneer Jamie Thomson's vision to enable scientists worldwide to easily access the power of iPSC technology, thus driving breakthroughs in human health," noted Bob Palay, CDI Chief Executive Officer.

To eliminate the variability introduced by a mouse cell feeder layer previously used during the culture of human iPS cells, researchers have adopted "feeder-free" media. However, existing feeder-free culture media contain more than 20 interactive ingredients, many of which, such as bovine serum albumin (BSA) and lipids, are highly uncharacterized and vary significantly from lot-to-lot.This leads to variability in iPS cell growth and differentiation and impedes the progress of disease studies and potential clinical applications.

Essential 8 Medium, manufactured in a Life Technologies current Good Manufacturing Practices (cGMP) facility, overcomes this barrier. In addition, BSA and other undesirable components have been removed from the media, thus reducing the number of ingredients to just eight well-characterized elements required to support efficient growth, eliminate variability, and enable large-scale production of human iPS cells.

"Essential 8 has far fewer variables, it's more straight-forward and a lot more reproducible," said Emile Nuwaysir, Ph.D., Chief Operating Officer and Vice President of Cellular Dynamics International. "If the goal is to make a billion cardiomyocytes a day, every day, you want to make sure they're all the same. That's virtually impossible using mouse embryonic fibroblasts and it's very difficult using the more complex, feeder-free media that were available before Essential 8."

Optimized for use with Essential 8 Medium, Vitronectin (VTN-N) is a defined, human protein-based substrate that further eliminates variability during iPS cell culture unlike most existing feeder-free media that requires the use of an undefined matrix derived from mouse tumor cells for cell attachment and growth. The combination of Essential 8 Medium and Vitronectin (VTN-N) provides a defined, culture system free of non-human components for robust, cost-effective and scalable iPS cell culture.

Life Technologies is also introducing the Episomal iPSC Reprogramming Vectors, which leverages non-viral, non-integrating technology to deliver six genes to initiate the reprogramming of human somatic cells, such as blood and skin cells, to iPS cells. A non-viral approach offers a key advantage: human-derived iPS cells have more relevance for patient-specific, disease research. Traditional viral-based methods, such as lentivirus or retrovirus, require integration into the host genome for replication and can disrupt the genome of the reprogrammed cells.

"The ability to reproducibly establish andculture iPS cells using defined reagent systems is key for the advancement of stem cell research, disease modeling and drug discovery," said Chris Armstrong Ph.D, General Manager and Vice President of Primary and Stem Cell Systems at Life Technologies. "The commercialization of these exciting new products serves that purpose and underscores our commitment to provide the most innovative and relevant workflow tools to our customers."

All three products were developed at the University of Wisconsin by Dr. James Thomson, whose lab pioneered embryonic stem cell research and much of the technology surrounding stem cell culturing conditions, in vitro differentiation and iPS cell generation.

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International Stem Cell Corporation Announces Marketing Plans for Its Wholly Owned Subsidiary Lifeline Skin Care

Posted: June 13, 2012 at 6:12 am

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

International Stem Cell Corporation (ISCO) (www.internationalstemcell.com) has announced new sales and marketing initiatives for its Lifeline Skin Care products (www.lifelineskincare.com). These efforts are designed to enable Lifeline to robustly, strategically and profitably grow the business.

Consumer Advertising

During June and July, new integrated advertising campaigns will be launched in three marketing channelsonline, in newspapers and magazines, and through direct mail. The campaigns will feature Lifelines innovative stem cell technology and proof of the brands potential: younger looking skin. Although the ads will eventually be national in reach, the first few months will be devoted to optimizing the creative approach, targeting, frequency, timing, positioning, offer and ROI.

Key Opinion Leader and Peer Group Influencer

Elizabeth K. Hale, MD, one of the nation's top dermatologists, is now endorsing Lifeline Skin Care to both consumer and trade audiences. Dr. Hale is an Associate Clinical Professor of Dermatology at New York University, a private practitioner and a guest of the Doctor Oz show, the Today Show and Good Morning America. During the week of June 4 she met with beauty editors for Prevention, Health, Town and Country, Allure, FoxNews.com and InStyle, to present Lifeline Skin Care and its unique technology. The endorsement of a leading dermatologist should not only enhance the credibility of the brand but increase its visibility.

Strategic Partners

Email campaigns through strategic partners have been very successful at marketing Lifeline products. To expand that effort, several new key opinion leaders have now agreed to endorse Lifeline Skin Care to their social networks, including Mrs. Jeri Thompson, a conservative spokesperson, radio and TV guest and advocate for non-embryonic stem cell research; and authors, experts and media personalities in the areas of women's health, yoga, cosmetic dentistry, and retirement planning. Many of these partners plan to market Lifeline through their social network (email marketing, blogs, Facebook, etc.) as well as through personal and radio appearances. Most of these campaigns will launch during the third quarter.

Professional Channels

During the week of June 12, Lifeline is launching two campaigns directed to 27,000 cosmetic dermatologists and day spas. These campaigns are focused on providing information to skin care professionals, including dermatologists and plastic surgeons, to understand and embrace the significance and value of stem cell extracts for skin rejuvenation.

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BGI, GE Healthcare team up on pioneering stem cell science projects

Posted: June 12, 2012 at 5:16 pm

Public release date: 12-Jun-2012 [ | E-mail | Share ]

Contact: Jia Liu liujia@genomics.cn BGI Shenzhen

Chalfont St. Giles, UK, and Shenzhen, China 12 June, 2012 GE Healthcare, the healthcare business of GE (NYSE: GE), and BGI, the world's largest genomics organization, jointly announced today a pioneering multi-year research collaboration in stem cell science. The objective of the collaboration is to help advance the potential global utility of stem cell-derived assays for use in drug discovery and toxicity testing by exploring the underlying genetic variation between ethnically diverse human stem cell lines. The collaboration was announced at a signing ceremony attended by Dr Amr Abid, General Manager Cell Technologies, GE Healthcare Life Sciences and Lin Fang, Vice President of BGI, Ye Yin, Deputy President of BGI, and Yutao Du, Deputy President of BGI.

The collaborating parties are initially undertaking two ground-breaking projects. Firstly, BGI is performing genome sequencing and epigenetic analysis on cardiomyocytes and hepatocytes supplied by GE Healthcare Life Sciences. The aim is to map out the genetic variation across an ethnically diverse range of stem cell lines and to examine the changes that occur during differentiation into specific cell types in order to increase the understanding of cell models used in drug development research. Secondly, GE Healthcare is providing BGI with an IN Cell Analyzer 2000 system, a research tool for high content cellular imaging analysis. Training on the IN Cell Analyzer will be provided to BGI, enabling it to investigate gene function for a library of previously sequenced cell types by overexpressing or blocking the activity of single genes and observing the effect in selected populations of cells.

Dr Amr Abid, General Manager Cell Technologies, GE Healthcare Life Sciences, said, "As the pharmaceutical industry seeks to reduce the cost of drug development and to bring more effective, safer drugs to market, the availability of more biologically relevant and predictive cell models is becoming increasingly important. Our long term vision is to help this process by developing a broad range of Cytiva stem-cell derived assays, to include cell types from a wide diversity of ethnic backgrounds. This is a big challenge and we are delighted to be working with such a prestigious institute as the BGI, with its significant resources and world-class capabilities in genomics and epigenomics. By working together, we will advance our understanding of different stem cell lines, which in turn may in the future help in the global drive to develop new, safer and more effective medicines."

Yutao Du, Deputy President of BGI, said, "The importance of high-throughput sequencing has been increasing rapidly in the areas of healthcare, agriculture, environment, and others. Genetic variation analysis of functional cells derived from embryonic stem cells may provide a promising cell model resource for drug development and cell therapy. We are grateful for this opportunity to join hands with an outstanding healthcare organization to push the boundaries of understanding in the field of stem cells. "

###

About GE Healthcare

GE Healthcare provides transformational medical technologies and services that are shaping a new age of patient care. Our broad expertise in medical imaging and information technologies, medical diagnostics, patient monitoring systems, drug discovery, biopharmaceutical manufacturing technologies, performance improvement and performance solutions services help our customers to deliver better care to more people around the world at a lower cost. In addition, we partner with healthcare leaders, striving to leverage the global policy change necessary to implement a successful shift to sustainable healthcare systems. Our "healthymagination" vision for the future invites the world to join us on our journey as we continuously develop innovations focused on reducing costs, increasing access and improving quality around the world. Headquartered in the United Kingdom, GE Healthcare is a unit of General Electric Company (NYSE: GE). Worldwide, GE Healthcare employees are committed to serving healthcare professionals and their patients in more than 100 countries. For more information about GE Healthcare, visit our website at http://www.gehealthcare.com.

About BGI

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Life Technologies and Cellular Dynamics International Partner for Global Commercialization of Novel Stem Cell …

Posted: June 12, 2012 at 2:21 pm

CARLSBAD, Calif., June 12, 2012 /PRNewswire/ -- Life Technologies Corporation (LIFE) today announced a partnership with Cellular Dynamics International (CDI), the world's largest producer of human cells derived from induced pluripotent stem (iPS) cells, to commercialize a set of three new products optimized to consistently develop and grow human iPS cells for both research and bioproduction.

The partnership marries CDI's leadership in human iPS cell development with Life Technologies' expertise in stem cell research tool manufacturing and global distribution network to make these novel technologies accessible to researchers around the world. Life Technologies' commercialization of Essential 8 Medium, Vitronectin (VTN-N), and Episomal iPSC Reprogramming Vectors addresses several challenges associated with developing relevant cells for use in a wide range of studies, from basic and translational research to drug discovery efforts. The effectiveness of these products is the focus of recent validation studies published in the journals Nature Methods and PLoS One.

"The launch of these new stem cell culture products furthers CDI founder and stem cell pioneer Jamie Thomson's vision to enable scientists worldwide to easily access the power of iPSC technology, thus driving breakthroughs in human health," noted Bob Palay, CDI Chief Executive Officer.

To eliminate the variability introduced by a mouse cell feeder layer previously used during the culture of human iPS cells, researchers have adopted "feeder-free" media. However, existing feeder-free culture media contain more than 20 interactive ingredients, many of which, such as bovine serum albumin (BSA) and lipids, are highly uncharacterized and vary significantly from lot-to-lot.This leads to variability in iPS cell growth and differentiation and impedes the progress of disease studies and potential clinical applications.

Essential 8 Medium, manufactured in a Life Technologies current Good Manufacturing Practices (cGMP) facility, overcomes this barrier. In addition, BSA and other undesirable components have been removed from the media, thus reducing the number of ingredients to just eight well-characterized elements required to support efficient growth, eliminate variability, and enable large-scale production of human iPS cells.

"Essential 8 has far fewer variables, it's more straight-forward and a lot more reproducible," said Emile Nuwaysir, Ph.D., Chief Operating Officer and Vice President of Cellular Dynamics International. "If the goal is to make a billion cardiomyocytes a day, every day, you want to make sure they're all the same. That's virtually impossible using mouse embryonic fibroblasts and it's very difficult using the more complex, feeder-free media that were available before Essential 8."

Optimized for use with Essential 8 Medium, Vitronectin (VTN-N) is a defined, human protein-based substrate that further eliminates variability during iPS cell culture unlike most existing feeder-free media that requires the use of an undefined matrix derived from mouse tumor cells for cell attachment and growth. The combination of Essential 8 Medium and Vitronectin (VTN-N) provides a defined, culture system free of non-human components for robust, cost-effective and scalable iPS cell culture.

Life Technologies is also introducing the Episomal iPSC Reprogramming Vectors, which leverages non-viral, non-integrating technology to deliver six genes to initiate the reprogramming of human somatic cells, such as blood and skin cells, to iPS cells. A non-viral approach offers a key advantage: human-derived iPS cells have more relevance for patient-specific, disease research. Traditional viral-based methods, such as lentivirus or retrovirus, require integration into the host genome for replication and can disrupt the genome of the reprogrammed cells.

"The ability to reproducibly establish andculture iPS cells using defined reagent systems is key for the advancement of stem cell research, disease modeling and drug discovery," said Chris Armstrong Ph.D, General Manager and Vice President of Primary and Stem Cell Systems at Life Technologies. "The commercialization of these exciting new products serves that purpose and underscores our commitment to provide the most innovative and relevant workflow tools to our customers."

All three products were developed at the University of Wisconsin by Dr. James Thomson, whose lab pioneered embryonic stem cell research and much of the technology surrounding stem cell culturing conditions, in vitro differentiation and iPS cell generation.

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Heart disease and stem-cell treatments: caught in a clinical stampede

Posted: June 12, 2012 at 11:16 am

A few years ago, concerns over these heart trials were voiced by a Norwegian professor, Harald Arnesen. He concluded in 2007 that they are not convincing and that one German team had achieved striking results only because the control group in its trial had done particularly badly. Prof Arnesen called for a moratorium on this kind of stem-cell therapy.

That still did not deter the clinicians. This January, another trial funded by the EU was announced the largest of all, with 3,000 heart-attack patients recruited from across Europe.

The idea behind the trials is straightforward. During a heart attack, a clogged blood vessel starves heart muscle of oxygen. Up to a billion heart muscle cells, called cardiomyocytes, can be damaged, and the body responds by replacing them with relatively inflexible scar tissue, which can lead to fatal heart failure. So why not implant stem cells that can grow into cardiomyocytes?

Stem cells, of course, come in many kinds: the embryonic variety have the potential to turn into all 200 cell types in the body. Adult stem cells, harvested from the patient, have a more limited repertoire: bone marrow stem cells generate blood cells, for example. So to claim, as was done in 2001, these bone marrow stem cells could turn into heart muscle was both surprising and exciting.

Analysis shows that, at best, the amount of blood pumped during a contraction of one heart chamber rose by 5 per cent after treatment. In a patient where heart efficiency has fallen to 30 per cent of normal, that could be significant but it is relatively meagre, none the less. And it turns out that this level of improvement results whatever the cells injected into the damaged muscle even if they have no prospect of forming cardiomyoctes.

Even the believers in the technique now agree that implanted cells exert a paracrine action, triggering a helpful inflammatory response or secreting chemicals that boost blood vessel formation. But were still waiting for convincing evidence that a patients lost heart muscle cells can be replaced.

Embryonic stem cells offer one route to that goal, though it is difficult to turn them into the right cell type reliably, and there are other risks, such as uncontrolled growths. Another option has come from work by Prof Richard Lee at the Harvard Stem Cell Institute, who has found that some adult stem cells can recruit other stem cells already in the heart to become cardiomyocytes.

Meanwhile, other fields of medicine that have seen more systematic research on stem cells are making real progress in using them for example, to treat Parkinsons, diabetes and macular degeneration. The lesson here is that, ultimately, it takes careful experiments, not belief, to make that huge leap from the laboratory to the hospital.

Roger Highfield is director of external affairs at the Science Museum Group

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Scientists grow living bone out of stem cells in bid to treat arthritis, osteoperosis and shattered limbs

Posted: June 12, 2012 at 11:14 am

By Daily Mail Reporter

PUBLISHED: 07:22 EST, 11 June 2012 | UPDATED: 07:53 EST, 11 June 2012

Hope: The technique of growing new bones could one day be used to replace serious breaks and treat degenerative illnesses

Scientists have successfully grown living bones in a laboratory using stem cells, in a technique that could in future be used to replace shattered limbs, treat osteoporosis and arthritis and fix defects such as cleft palate.

The researchers took around a month to transform stem cells originally taken from fat tissue into sections of fully-formed bone up to several centimetres long.

Standard bone grafts involve two procedures, to cut bone from elsewhere in the patient's body before transplanting it into the damaged area, which carry the risk of infection and complications. Bone can also be obtained from donations, but this brings the chance of rejection.

The new method would allow bones to be custom made to shape outside the body, using the patients own stem cells, removing the need for a potentially traumatic operation and reducing the likelihood of rejection.

So far the research has been carried out only on animals but a patient trial is planned for later this year.

The Israeli technology, developed by biotech company Bonus BioGroup and researchers at the Technion Institute of Research, involves growing the bone to fit the exact shape and size of the damaged area.

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Growing Bone from Stem Cells in Fat Could End Painful Graft Operations

Posted: June 12, 2012 at 11:14 am

Durham, NC (PRWEB) June 11, 2012

Bone grafts grown from purified stem cells originating from fat could lead to a more efficient way to regenerate bone and end the painful operations needed to collect a patients own bone for grafting. The results could have significant impact on those suffering from severe bone injuries or disease.

In a study published in the June issue of STEM CELLS Translational Medicine, researchers were able to demonstrate the potential of a population of stem cells found in human fat to generate bone. They also identified a new factor to stimulate bone growth. The team was made up of scientists from the UCLA-Orthopaedic Hospital Department of Orthopaedic Surgery, the Orthopaedic Hospital Research Center, and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at the University of California-Los Angeles (UCLA).

Researchers have long recognized the potential of stem cells harvested from fat which they call adipose-derived stem cells or ASCs in bone engineering. For one thing, stem cells are more easily obtainable from fat than from bone marrow, which also contains stem cells, plus ASCs have already been used successfully to heal skeletal defects in animals. And while the current gold standard for collecting bone for grafting autograft bone, which is that taken from the patient himself has significant disadvantages, including the potential for complications arising from the extended operating time needed to collect it, harvesting stem cells from fat tissue is painless and poses minimal risk to the patient.

However, there are several obstacles to the use of ASCs, including the risk of infection and genetic instability when the cells are isolated and expanded in the lab. As an alternative, researchers have looked at the possibility of using stromal vascular fraction (SVF), which comes from lipoaspirate, the byproduct of a liposuction.

SVF contains a variety of cells, including smooth muscle cells, fibroblasts, adult stem cells and more. In addition, it contains blood cells from the capillaries supplying the fat cells. The SVF has the advantage of being rapidly available (there is no need for culture isolation), but it falls significantly short for bone growth, with studies showing it yields poor and unreliable bone formation.

The main problem is this makeup of heterogeneous cell population, which can lead to unreliable bone formation, Chia Soo, M.D., explained. She and Bruno Pault, Ph.D., and Kang Ting, D.M.D., D.Med.Sc., were the senior corresponding investigators on the study, funded by the California Institute of Regenerative Medicine (CIRM).

So the UCLA team decided to see what would happen if they purified the SVF cells to reduce their inherent heterogeneity and obtain a safer, more efficient stem cell-based therapeutic. Their goal was to isolate a population of stem cells known as perivascular stem cells (PSCs) that surround blood vessels. The team then took the bone grafts grown from the human PSCs and implanted them in mice to compare their bone-forming capacity with that of traditionally derived SVF.

The results exceeded expectation.

The purified human PSCs formed significantly more bone in comparison to traditionally derived SVF by all parameters, Aaron James, M.D., the studys lead author, said. This is true in terms of potency, identity and purity.

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Clues found to way embryonic kidney maintains its fleeting stem cells

Posted: June 12, 2012 at 11:14 am

ScienceDaily (June 11, 2012) Studying mice and humans, researchers at Washington University School of Medicine in St. Louis and their collaborators in Paris have identified two proteins that are required to maintain a supply of stem cells in the developing kidney.

In the presence of the two proteins, FGF9 and FGF20, mouse kidney stem cells stayed alive outside the body longer than previously reported. Though the cells were maintained only five days (up from about two), the work is a small step toward the future goal of growing kidney stem cells in the lab.

In the developing embryo, these early stem cells give rise to adult cells called nephrons, the blood filtration units of the kidneys.

The results appear online June 11 in Developmental Cell.

"When we are born, we get a certain allotment of nephrons," says Raphael Kopan, PhD, the Alan A. and Edith L. Wolff Professor of Developmental Biology. "Fortunately, we have a large surplus. We can donate a kidney -- give away 50 percent of our nephrons -- and still do fine. But, unlike our skin and gut, our kidneys can't build new nephrons."

The skin and the gut have small pools of stem cells that continually renew these organs throughout life. Scientists call such pools of stem cells and their support system a niche. During early development, the embryonic kidney has a stem cell niche as well. But at some point before birth or shortly after, all stem cells in the kidney differentiate to form nephrons, leaving no self-renewing pool of stem cells.

"In other organs, there are cells that specifically form the niche, supporting the stem cells in a protected environment," Kopan says. "But in the embryonic kidney, it seems the stem cells form their own niche, making it a bit more fragile. And the signals and conditions that lead the cells to form this niche have been elusive."

Surprisingly, recent clues to the signals that maintain the embryonic kidney's stem cell niche came from studies of the inner ear. David M. Ornitz, MD, PhD, the Alumni Endowed Professor of Developmental Biology, investigates FGF signaling in mice. Earlier this year, Ornitz and his colleagues published a paper in PLoS Biology showing that FGF20 plays an important role in inner ear development.

"Mice without FGF20 are profoundly deaf," Ornitz says. "While they are otherwise viable and healthy, in some cases we noticed that their kidneys looked small."

Past work from his own lab and others suggested that FGF9, a close chemical cousin of FGF20, might also participate in kidney development. FGF20 and FGF9 are members of a family of proteins known as fibroblast growth factors. In general, members of this family are known to play important and broad roles in embryonic development, tissue maintenance, and wound healing. Mice lacking FGF9 have defects in development of the male urogenital tract and die after birth due to defects in lung development.

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Stanford researcher identifies unusual 'altruistic' stem cell behavior with possible link to cancer

Posted: June 12, 2012 at 11:14 am

Public release date: 11-Jun-2012 [ | E-mail | Share ]

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center

STANFORD, Calif. When most groups of mammalian cells are faced with a shortage of nutrients or oxygen, the phrase "every man for himself" is more apt than "all for one, one for all." Unlike colonies of bacteria, which often cooperate to thrive as a group, mammalian cells have never been observed to help one another out. But a new study led by a researcher at the Stanford University School of Medicine has shown that certain human embryonic stem cells, in times of stress, produce molecules that not only benefit themselves, but also help nearby cells survive.

"Altruism has been reported among bacterial populations and among humans and other animals, like monkeys and elephants," said Stanford postdoctoral scholar Bikul Das, MBBS, PhD. "But in mammalian cells at the cellular level the idea of altruism has never been described before." Das is the lead author of a paper, to be published online June 11 in Stem Cells, documenting altruistic behavior by human embryonic stem cells, or hESCs.

While altruism is generally thought of as a virtue, it can have a downside for hESCs: The altruistic cells appear to be more prone to accumulating mutations, a sign that they could lead to cancers. A better understanding of hESC altruism could provide new insights into cancer therapies, as well as improving scientists' ability to develop safe and effective stem cell treatments for other diseases.

The finding arose from Das' research into how hESCs react to low-oxygen environments, important because many cancerous tumors are low in oxygen. Embryonic stem cells have the capability to develop into many different cell types through a process called differentiation. Das found that when hESCs were placed for 24 hours in an environment with only one-tenth of a percent of oxygen (the air we breathe, by comparison, is almost 21 percent oxygen), free-radical molecules were generated that began causing internal damage in some cells. Ninety percent of the hESCs differentiated into other cell types or died, with only 10 percent maintaining their so-called "stemness," meaning they retained their ability to develop into any type of cell.

Das wanted to know what set these more hearty cells apart and so began sorting them based on what molecules they contained.

Das and his colleagues discovered that of the embryonic stem cells that had survived the oxygen deprivation, half had high levels of HIF2-alpha (a protein that turns up the production of antioxidant molecules) and low levels of p53 (a protein that normally encourages cells to die when they have too much DNA damage). These levels of HIF2-alpha and p53 are enough, Das showed, to keep the cells from differentiating by turning off cellular pathways typically involved in the process.

But the other half of the stem cells that had kept their "stemness" had relatively normal levels of HIF2-alpha and p53, he and his colleagues report in their paper. There was no clear explanation as to how they would remain undifferentiated without the help of high HIF2-alpha and low p53 unless the other cells were helping them out.

"When I saw this data, I began to suspect that maybe there was altruism going on," said Das.

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Unusual 'altruistic' stem cell behavior with possible link to cancer identified

Posted: June 12, 2012 at 11:14 am

ScienceDaily (June 11, 2012) When most groups of mammalian cells are faced with a shortage of nutrients or oxygen, the phrase "every man for himself" is more apt than "all for one, one for all." Unlike colonies of bacteria, which often cooperate to thrive as a group, mammalian cells have never been observed to help one another out. But a new study led by a researcher at the Stanford University School of Medicine has shown that certain human embryonic stem cells, in times of stress, produce molecules that not only benefit themselves, but also help nearby cells survive.

"Altruism has been reported among bacterial populations and among humans and other animals, like monkeys and elephants," said Stanford postdoctoral scholar Bikul Das, MBBS, PhD. "But in mammalian cells -- at the cellular level -- the idea of altruism has never been described before." Das is the lead author of a paper, published online June 11 in Stem Cells, documenting altruistic behavior by human embryonic stem cells, or hESCs.

While altruism is generally thought of as a virtue, it can have a downside for hESCs: The altruistic cells appear to be more prone to accumulating mutations, a sign that they could lead to cancers. A better understanding of hESC altruism could provide new insights into cancer therapies, as well as improving scientists' ability to develop safe and effective stem cell treatments for other diseases.

The finding arose from Das' research into how hESCs react to low-oxygen environments, important because many cancerous tumors are low in oxygen. Embryonic stem cells have the capability to develop into many different cell types through a process called differentiation. Das found that when hESCs were placed for 24 hours in an environment with only one-tenth of a percent of oxygen (the air we breathe, by comparison, is almost 21 percent oxygen), free-radical molecules were generated that began causing internal damage in some cells. Ninety percent of the hESCs differentiated into other cell types or died, with only 10 percent maintaining their so-called "stemness," meaning they retained their ability to develop into any type of cell.

Das wanted to know what set these more hearty cells apart and so began sorting them based on what molecules they contained.

Das and his colleagues discovered that of the embryonic stem cells that had survived the oxygen deprivation, half had high levels of HIF2-alpha (a protein that turns up the production of antioxidant molecules) and low levels of p53 (a protein that normally encourages cells to die when they have too much DNA damage). These levels of HIF2-alpha and p53 are enough, Das showed, to keep the cells from differentiating by turning off cellular pathways typically involved in the process.

But the other half of the stem cells that had kept their "stemness" had relatively normal levels of HIF2-alpha and p53, he and his colleagues report in their paper. There was no clear explanation as to how they would remain undifferentiated without the help of high HIF2-alpha and low p53 -- unless the other cells were helping them out.

"When I saw this data, I began to suspect that maybe there was altruism going on," said Das.

To test the theory, Das and his colleagues at the University of Toronto, where he began the work as a graduate student, let the cells with high levels of HIF2-alpha and low levels of p53 soak in a cell culture medium for 24 hours. Then, he removed the cells and added the other half -- those that didn't have high HIF2-alpha and low p53. Sure enough, when the mixture was deprived of oxygen, the cells retained their stemness. Molecules in the liquid had some property that kept them from differentiating. The team discovered that the important molecule in the liquid is an antioxidant called glutathione.

Scientists had previously shown that when embryonic stem cells are under stress, levels of HIF2-alpha and p53 increase and most cells differentiate or die. What makes this study unusual is that Das and colleagues were able to isolate the altruistic cells that exhibit low levels of p53, which helps them to escape death or differentiation.

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