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A*STAR scientists make groundbreaking discovery on stem cell regulation

Posted: March 1, 2012 at 7:08 pm

Public release date: 29-Feb-2012 [ | E-mail | Share ]

Contact: Ong Siok Ming ong_siok_ming@a-star.edu.sg 65-682-66254 Agency for Science, Technology and Research (A*STAR), Singapore

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

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

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

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

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

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

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UCLA Scientists Identify Cell and Signaling Pathway that Regulates the Placental Blood Stem Cell Niche

Posted: March 1, 2012 at 7:08 pm

Newswise UCLA stem cell researchers have discovered a critical placental niche cell and signaling pathway that prevent blood precursors from premature differentiation in the placenta, a process necessary for ensuring proper blood supply for an individuals lifetime.

The placental niche, a stem cell safe zone, supports blood stem cell generation and expansion without promoting differentiation into mature blood cells, allowing the establishment of a pool of precursor cells that provide blood cells for later fetal and post-natal life, said study senior author Dr. Hanna Mikkola, an associate professor of molecular cell and developmental biology and a researcher at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Mikkola and her team found that PDGF-B signaling in trophoblasts, specialized cells of the placenta that facilitate embryo implantation and gas and nutrient exchanges between mother and fetus, is vital to maintaining the unique microenvironment needed for the blood precursors. When PDGF-B signaling is halted, the blood precursors differentiate prematurely, creating red blood cells in the placenta, Mikkola said.

The study, done in mouse models, appears March 1, 2012, in the peer-reviewed journal Developmental Cell.

We had previously discovered that the placenta provides a home for a large supply of blood stem cells that are maintained in an undifferentiated state. We now found that, by switching off one signaling pathway, the blood precursors in the placenta start to differentiate into red blood cells, Mikkola said. We learned that the trophoblasts act as powerful signaling centers that govern the niche safe zone.

The study found that the PDGF-B signaling in the trophoblasts is suppressing production of Erythropoietin (EPO), a cytokine that controls red blood cell differentiation.

When PDGF-B signaling is lost, excessive amounts of EPO are produced in the placenta, which triggers differentiation of red blood cells in the placental vasculature, said Akanksha Chhabra, study first author and a post-doctoral fellow in Mikkolas lab.

Mikkola and Chhabra used mouse models in which the placental structure was disrupted so they could observe what cells and signaling pathways were important components of the niche.

The idea was, if we mess up the home where the blood stem cells live, how do these cells respond to the altered environment, Chhabra said. We found that it was important to suppress EPO where blood stem cell expansion is desired and to restrict its expression to areas where red blood cell differentiation should occur.

The finding, Chhabra said, was exciting in that one single molecular change was enough to change the function of an important blood stem cell niche.

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QF honours stem cell researchers

Posted: March 1, 2012 at 3:19 am

Research on preventing breast cancer recurrence, using organ regeneration to combat obesity-related diseases, and enabling vascular repair for patients suffering from cardiovascular disease has received awards at the ongoing Qatar International Conference on Stem Cell Science and Policy 2012. The award ceremony hosted by Qatar Foundation for Education, Science and Community Development at Qatar National Convention Centre recognised two professional researchers and one student researcher for excellence in stem cell research, with the research exhibited through poster presentations during the conference. Leaders from QF and top figures in the stem cell science and ethics field congratulated the award recipients. Dr Abdelali Haoudi, vice president for research at QF, said: We are truly impressed with the research presented this year in poster presentations, as well as in the oral presentations and panel discussions taking place throughout the conference. He added: Through this conference, we hope to drive further exploration in this field that will lead to even greater progress in applying stem cell science to prevent and treat diseases afflicting communities both in Qatar and around the world. The three posters were selected for recognition by a review committee, comprised of academics, researchers and scientists, including Nobel Laureates and international experts. Pegah Ghiabi, a researcher at the Stem Cell & Microenvironment Laboratory at Weill Cornell Medical College in Qatar, received an award for her poster presentation on research into therapy to inhibit the cancer stem cell population to prevent the recurrence of breast cancer. Research by Lara Bou-Khzam of the McGill University Health Centre Research Institute in Montreal, Canada, also received recognition. The poster focused on her stem cell research towards vascular repair for patients suffering from cardiovascular disease, one of the worlds leading causes of mortality. The final award was presented to Dr Heba al-Siddiqui for her research at the Harvard Stem Cell Institute on preventing chronic obesity-related diseases through tissue engineering and organ regeneration. Dr al-Siddiqui is a trainee in the Qatar Science Leadership Programme, a QF initiative aimed at equipping rising Qatari generations for leading roles in the countrys scientific and research endeavours. The Qatar International Conference on Stem Cell Science and Policy, organised through a partnership between QF and the James A. Baker III Institute of Public Policy at Rice University, will conclude today. The four-day conference, which featured expert panels and presentations on the latest opportunities and challenges in stem cell research, was attended by top figures in the fields of science, ethics and policy of stem cell research from across the Middle East region and around the world.

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Nuvilex Reveals Goldman Small Cap Research Cites Groundbreaking Cancer Therapy in Updating Buy Recommendation

Posted: February 29, 2012 at 11:52 pm

SILVER SPRING, Md.--(BUSINESS WIRE)--

Nuvilex, Inc. (OTCQB:NVLX), an emerging biotechnology provider of cell and gene therapy solutions, announced today Goldman Small Cap Research has reissued its buy recommendation on Nuvilex with a short term price target of $0.50 per share.

According to the research report prepared by Goldman, The current share price represents but a fraction of its true value, in our view. With recently increased interest and valuation in the pancreatic cancer treatment arena, we believe that Nuvilex is worth $0.20 just on the oncology therapies alone and that the shares will reach $0.50 in the next six months. Looking ahead, as milestone events occur, $1.00 per share is within reach over the next 12-18 months.

Goldman bases this value projection, in part, on the pending acquisition of SG Austria assets, and with it complete control over the cell encapsulation technology that forms the backbone of Nuvilexs planned biotechnology development. The report states in part the following:

Following execution of the SG Austria asset acquisition, we expect to see a flurry of events and progress on the development side which will serve as catalysts, including when management submits its protocol for the next stage pancreatic cancer trial. We would not be surprised to see the stock break through the $0.50 price on such news as well as progress on the next stage of trials for other therapies.

One reason we are so convinced of the great buying opportunity is the fact that pancreatic cancer treatments are currently at the forefront of the biotech space and are enjoying very high valuations. Although Nuvilex is a not a drug producer, but an existing therapy enhancer through the use of its live cell encapsulation enhancement platform, the timing of these milestone events could not be better for Nuvilex and a re-valuation of its offering.

The Goldman report also compares alternative oncology therapies, including Gemzar from Threshold Pharmaceuticals and Merrimack Pharmaceuticals drug encapsulation technology, noting that, contrary to these treatments, the Nuvilex live-cell encapsulation technology is not limited to one specific use, but can be adapted to use for a host of cell types. The report states, Its difficult to compare apples-to-apples in this space as Nuvilex is the only firm utilizing live-cell encapsulation therapy for cancer, while all the other treatments are based upon a particular drug usage. Contrasting the results of different Phase II clinical trials, the Goldman report comments that the pancreatic cancer therapy, based on completed Phase 1/2 data, appears to have yielded statistically greater results than competing technologies.

Commenting on The Goldman Report, Nuvilex Chief Executive Officer, Dr. Robert Ryan, stated, The report did an excellent job highlighting the value and capabilities of our cell encapsulation technology, not just for cancer therapy, but also for the vast array of treatments where live-cell encapsulation can aid multiple diseases. In the case of the completed cancer trials, it generated superior results with lower drug dosages, and reduced chemotherapeutic side effects. As we move forward with diabetes and stem cell therapy treatments, we are confident our success will, as Goldman predicts prompt leaders in multiple treatment segments to partner with Nuvilex in order to maintain their respective market shares.

Investors are recommended to study the Goldman Research Report for a detailed review and valuation methodology regarding Nuvilex.

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QF honours stem cell researchers

Posted: February 29, 2012 at 11:52 pm

Research on preventing breast cancer recurrence, using organ regeneration to combat obesity-related diseases, and enabling vascular repair for patients suffering from cardiovascular disease has received awards at the ongoing Qatar International Conference on Stem Cell Science and Policy 2012. The award ceremony hosted by Qatar Foundation for Education, Science and Community Development at Qatar National Convention Centre recognised two professional researchers and one student researcher for excellence in stem cell research, with the research exhibited through poster presentations during the conference. Leaders from QF and top figures in the stem cell science and ethics field congratulated the award recipients. Dr Abdelali Haoudi, vice president for research at QF, said: We are truly impressed with the research presented this year in poster presentations, as well as in the oral presentations and panel discussions taking place throughout the conference. He added: Through this conference, we hope to drive further exploration in this field that will lead to even greater progress in applying stem cell science to prevent and treat diseases afflicting communities both in Qatar and around the world. The three posters were selected for recognition by a review committee, comprised of academics, researchers and scientists, including Nobel Laureates and international experts. Pegah Ghiabi, a researcher at the Stem Cell & Microenvironment Laboratory at Weill Cornell Medical College in Qatar, received an award for her poster presentation on research into therapy to inhibit the cancer stem cell population to prevent the recurrence of breast cancer. Research by Lara Bou-Khzam of the McGill University Health Centre Research Institute in Montreal, Canada, also received recognition. The poster focused on her stem cell research towards vascular repair for patients suffering from cardiovascular disease, one of the worlds leading causes of mortality. The final award was presented to Dr Heba al-Siddiqui for her research at the Harvard Stem Cell Institute on preventing chronic obesity-related diseases through tissue engineering and organ regeneration. Dr al-Siddiqui is a trainee in the Qatar Science Leadership Programme, a QF initiative aimed at equipping rising Qatari generations for leading roles in the countrys scientific and research endeavours. The Qatar International Conference on Stem Cell Science and Policy, organised through a partnership between QF and the James A. Baker III Institute of Public Policy at Rice University, will conclude today. The four-day conference, which featured expert panels and presentations on the latest opportunities and challenges in stem cell research, was attended by top figures in the fields of science, ethics and policy of stem cell research from across the Middle East region and around the world.

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Stem-Cell Therapy Takes Off in Texas

Posted: February 29, 2012 at 10:45 pm

By David Cyranoski of Nature magazine

With Texas pouring millions of dollars into developing adult stem-cell treatments, doctors there are already injecting paying customers with unproven preparations, supplied by an ambitious new company.

The US Food and Drug Administration (FDA) has not approved any such stem-cell treatment for routine clinical use, although it does sanction them for patients enrolled in registered clinical trials. Some advocates of the treatments argue, however, that preparations based on a patient's own cells should not be classed as drugs, and should not therefore fall under the FDA's jurisdiction.

There are certainly plenty of people eager to have the treatments. Texas governor Rick Perry, for instance, has had stem-cell injections to treat a back complaint, and has supported legislation to help create banks to store patients' harvested stem cells.

One company that has benefited from this buoyant climate is Celltex Therapeutics, which "multiplies and banks" stem cells derived from people's abdominal fat, according to chairman and chief executive David Eller. Its facility in Sugar Land, just outside Houston, opened in December 2011 and houses the largest stem-cell bank in the United States.

Celltex was founded by Eller and Stanley Jones, the orthopaedic surgeon who performed Perry's procedure, and it uses technology licensed from RNL Bio in Seoul. Because clinical use of adult-stem-cell treatments are illegal in South Korea, RNL has since 2006 sent more than 10,000 patients to clinics in Japan and China to receive injections.

Celltex says that although it processes and banks cells, it does not carry out stem-cell injections. It declined to answer Nature's questions about whether its cells have been used in patients. But there is evidence that the company is involved in the clinical use of the cells on US soil, which the FDA has viewed as illegal in other cases.

Public hype

In addition to the publicity surrounding Perry's treatment, a woman named Debbie Bertrand has been blogging about her experiences during a five-injection treatment with cells prepared at Celltex. Her blog (http://debbiebertrand.blogspot.com) hosts photographs of herself alongside Jones; Jennifer Novak, a Celltex nurse; Jeong Chan Ra, chief executive of RNL Bio; and her doctor, Jamshid Lotfi, a neurologist who works for the United Neurology clinic in Houston. Another photo is captioned: "My cells are being processed in here for my next infusion!!!" A third shows Bertrand, Lotfi and a physician called Matthew Daneshmand, who is, according to the caption, injecting Bertrand's stem cells into an intravenous drip, ready for the infusion. Nature has been unable to contact Bertrand.

Lotfi says that he has administered cells processed by Celltex to more than 20 people. "Five or six" -- including Bertrand -- have multiple sclerosis and "four or five" have Parkinson's disease, he says. Lotfi explains that patients sign up for treatment by contacting Novak, and that cells are prepared by removing about five grams of fat -- containing roughly 100,000 mesenchymal stem cells -- from the patient's abdomen. Over a three-week period, the cells are cultured until they reach about 800 million cells. Lotfi says that patients get at least three injections of 200 million cells each, and that the cells do not take effect for a few months. According to Lotfi, Celltex charges US$7,000 per 200 million cells, and pays Lotfi $500 per injection.

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Children improve in rare disorder with own stem cells

Posted: February 29, 2012 at 6:55 pm

London, Feb 29 (IANS) Children shot with their own stem cells, for the very first time in a rare immune disorder, have shown improvement.

The condition, known as X-CGD, is caused by faulty genes. Doctors were able to take a sample of the children's stem cells, manipulate them in the lab and reintroduce them. This gave the children a working copy of the faulty gene and their condition improved, enabling them to temporarily fight off infections.

It is the third immune disorder that doctors at Great Ormond Street Hospital have successfully tackled. The others were the life-threatening conditions, X-SCID and ada-SCID, and 90 percent of treated children have improved, with some showing signs that their immune system has been normalised for good.

Remy Helbawi, 16, from South London, was the first child with X-CGD to be treated. The condition only affects boys and means that while his body produces the white blood cells to fight viruses it does not have the correct cells to fight off bacterial or fungal infections, The Telegraph reports.

The resulting infections can be life-threatening. Up until now the only treatment has been a bone marrow transplant which would offer a permanent cure.

Remy's brother who also had the disease was found a bone marrow match and was successfully treated that way but no match has been found for Remy and a serious lung infection was threatening his life.

Remy said: "Until I was 10 I had the same life as anyone else, except I had eczema a lot of the time. I didn't have a fungal infection until about ten, but when I got my first fungal infection my life changed. I missed a lot of school, I had lots of tests and was in hospital. I would get exhausted after climbing stairs."

Before undergoing the gene therapy, Remy had to have chemotherapy which made his hair fall out and he was kept in isolation for a month.

Remy's nurse Helen Braggins said: "Remy had been unwell for last two years and began to miss school. He had significant fungal lung disease in January of last year, which was getting worse. Without some radical treatment intervention, Remy would not have survived and was becoming increasingly short of breath."

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Ovarian Stem Cells Holds Promise for Infertile Women: Study

Posted: February 29, 2012 at 6:55 pm

Researchers at the Massachusetts General Hospital (MGH) have isolated egg producing stem cells from human ovarian tissues.

Scientists at the Vincent Center for Reproductive Biology, MGH used a special fluorescence-activated cell sorting protocol in mice models to grow new eggs from isolated stem cells.

The new study is seen as a precursor to solving fertility issues in women of reproductive ages. If made viable, the study could benefit young women undergoing cancer therapy and older women who have to resort to egg donors.

The current breakthrough challenges the widely-accepted notion that while men generate sperms throughout life, women are born with a fixed supply of eggs that deplete with age and are finally exhausted at menopause.

The current research, published in the March issue of Nature Medicine is a follow-up on an earlier landmark 2004 Nature paper suggesting that female mammals have the capability of producing egg cells throughout their adult reproductive stages.

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"The discovery of oocyte precursor cells in adult human ovaries, coupled with the fact that these cells share the same characteristic features of their mouse counterparts that produce fully functional eggs, opens the door for development of unprecedented technologies to overcome infertility in women and perhaps even delay the timing of ovarian failure," said Jonathan Tilly, lead researcher and Director for Reproductive Biology at the MGH Vincent Department of Obstetrics and Gynecology.

To examine their arguments, the researchers injected green fluorescent protein (GFP)-labeled mouse oocyte-producing stem cells (OSCs) into the ovaries of normal adult mice. Several months later, the recipient mouse ovaries showed the presence of follicles containing oocytes (immature egg cells) with and without the marker protein. Similar GFP-labeled and unlabeled oocytes were observed in cell clusters flushed from the animals' oviducts after induced ovulation.

The GFP-labeled mouse eggs were fertilized in the lab to produce embryos that went on to the hatching blastocyst cell reproductive stages, indicating potential for normal egg cell development.

According to Tilly, "In this paper we provide the three key pieces of evidence requested by those who have been skeptical of our previous work."We developed and extensively validated a cell-sorting protocol to reliably purify OSCs from adult mammalian ovaries, proving once again that these very special cells exist. We tested the function of mouse oocytes produced by these OSCs and showed that they can be fertilized to produce healthy embryos. And we identified and characterized an equivalent population of oocyte-producing stem cells isolated from adult human ovaries", he added.

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Children improve in rare disorder with own stem cells

Posted: February 29, 2012 at 1:24 pm

London, Feb 29 (IANS) Children shot with their own stem cells, for the very first time in a rare immune disorder, have shown improvement.

The condition, known as X-CGD, is caused by faulty genes. Doctors were able to take a sample of the children's stem cells, manipulate them in the lab and reintroduce them. This gave the children a working copy of the faulty gene and their condition improved, enabling them to temporarily fight off infections.

It is the third immune disorder that doctors at Great Ormond Street Hospital have successfully tackled. The others were the life-threatening conditions, X-SCID and ada-SCID, and 90 percent of treated children have improved, with some showing signs that their immune system has been normalised for good.

Remy Helbawi, 16, from South London, was the first child with X-CGD to be treated. The condition only affects boys and means that while his body produces the white blood cells to fight viruses it does not have the correct cells to fight off bacterial or fungal infections, The Telegraph reports.

The resulting infections can be life-threatening. Up until now the only treatment has been a bone marrow transplant which would offer a permanent cure.

Remy's brother who also had the disease was found a bone marrow match and was successfully treated that way but no match has been found for Remy and a serious lung infection was threatening his life.

Remy said: "Until I was 10 I had the same life as anyone else, except I had eczema a lot of the time. I didn't have a fungal infection until about ten, but when I got my first fungal infection my life changed. I missed a lot of school, I had lots of tests and was in hospital. I would get exhausted after climbing stairs."

Before undergoing the gene therapy, Remy had to have chemotherapy which made his hair fall out and he was kept in isolation for a month.

Remy's nurse Helen Braggins said: "Remy had been unwell for last two years and began to miss school. He had significant fungal lung disease in January of last year, which was getting worse. Without some radical treatment intervention, Remy would not have survived and was becoming increasingly short of breath."

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Children improve in rare disorder with own stem cells

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Ovarian Stem Cells Holds Promise for Infertile Women: Study

Posted: February 29, 2012 at 1:24 pm

Researchers at the Massachusetts General Hospital (MGH) have isolated egg producing stem cells from human ovarian tissues.

Scientists at the Vincent Center for Reproductive Biology, MGH used a special fluorescence-activated cell sorting protocol in mice models to grow new eggs from isolated stem cells.

The new study is seen as a precursor to solving fertility issues in women of reproductive ages. If made viable, the study could benefit young women undergoing cancer therapy and older women who have to resort to egg donors.

The current breakthrough challenges the widely-accepted notion that while men generate sperms throughout life, women are born with a fixed supply of eggs that deplete with age and are finally exhausted at menopause.

The current research, published in the March issue of Nature Medicine is a follow-up on an earlier landmark 2004 Nature paper suggesting that female mammals have the capability of producing egg cells throughout their adult reproductive stages.

Like us on Facebook

"The discovery of oocyte precursor cells in adult human ovaries, coupled with the fact that these cells share the same characteristic features of their mouse counterparts that produce fully functional eggs, opens the door for development of unprecedented technologies to overcome infertility in women and perhaps even delay the timing of ovarian failure," said Jonathan Tilly, lead researcher and Director for Reproductive Biology at the MGH Vincent Department of Obstetrics and Gynecology.

To examine their arguments, the researchers injected green fluorescent protein (GFP)-labeled mouse oocyte-producing stem cells (OSCs) into the ovaries of normal adult mice. Several months later, the recipient mouse ovaries showed the presence of follicles containing oocytes (immature egg cells) with and without the marker protein. Similar GFP-labeled and unlabeled oocytes were observed in cell clusters flushed from the animals' oviducts after induced ovulation.

The GFP-labeled mouse eggs were fertilized in the lab to produce embryos that went on to the hatching blastocyst cell reproductive stages, indicating potential for normal egg cell development.

According to Tilly, "In this paper we provide the three key pieces of evidence requested by those who have been skeptical of our previous work."We developed and extensively validated a cell-sorting protocol to reliably purify OSCs from adult mammalian ovaries, proving once again that these very special cells exist. We tested the function of mouse oocytes produced by these OSCs and showed that they can be fertilized to produce healthy embryos. And we identified and characterized an equivalent population of oocyte-producing stem cells isolated from adult human ovaries", he added.

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Ovarian Stem Cells Holds Promise for Infertile Women: Study

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