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How adult fly testes keep from changing into ovaries

By adminNovember 13, 2014Stem Cell Medical Center

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New research in flies shows how cells in adult reproductive organs maintain their sexual identity. The study, publishing online on November 13 in the Cell Press journal Developmental Cell, also identified a mutation that can switch the cells' sexual identity. The findings could lead to new insights on how to alter cells for therapeutic purposes.

Sperm and eggs are made from germ cells, but instructions from their neighboring support cellscalled somatic cellsare also essential for their development. By studying the formation of sperm in fruit flies, which is remarkably similar to the process that occurs in people, investigators serendipitously found a mutation that gave testes a very unusual appearance. "Rather than becoming sperm, germ cells were stuck at an early stage, and they were surrounded by support cells that looked suspiciously like those belonging in an ovary," says senior author Dr. Erika Matunis of The Johns Hopkins School of Medicine. Her research team found that the mutation blocked the function of a specific gene in the stem cells that becomes support cells in the testis, causing the fruit flies to change from a male to a female identity.

The research is the first to show that adult stem cells actively maintain their sexual identity. The mutation the investigators found causes the stem cells in males to switch their sexual identities and start making support cells that belong in the ovary. This ultimately derails the production of sperm. "The molecules that govern this process are highly conserved, which suggests that similar mechanisms could operate in human testes," says Matunis.

The changes seen in this study are an example of transdifferentiation, or the conversion from one cell type to another. The topic is of considerable interest because promoting transdifferentiation in a directed manner may be useful for regenerating damaged organs or tissues. Doing so will require a thorough understanding of how cell fate conversions are regulated. "We are excited to have a powerful genetic system for studying transdifferentiation of stem cells at the mechanistic level," says Matunis. The research might also provide insights into how cells transform from a normal state to a cancerous one.

Explore further: Surprise: Lost stem cells naturally replaced by non-stem cells, fly research suggests

More information: Developmental Cell, Ma et al.: "The Jak-STAT target Chinmo prevents sex transformation of adult stem cells in the Drosophila testis niche" http://www.cell.com/developmental-cel 1534-5807(14)00628-5

Journal reference: Developmental Cell

Provided by Cell Press

Johns Hopkins researchers have discovered an unexpected phenomenon in the organs that produce sperm in fruit flies: When a certain kind of stem cell is killed off experimentally, another group of non-stem cells can come out ...

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How adult fly testes keep from changing into ovaries

Tumor suppressor also inhibits key property of stem cells, Stanford researchers say

By adminNovember 13, 2014Uncategorized

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13-Nov-2014

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

A protein that plays a critical role in preventing the development of many types of human cancers has been shown also to inhibit a vital stem cell property called pluripotency, according to a study by researchers at the Stanford University School of Medicine.

Blocking expression of the protein, called retinoblastoma, in mouse cells allowed the researchers to more easily transform them into what are known as induced pluripotent stem cells, or iPS cells. Pluripotent is a term used to describe a cell that is similar to an embryonic stem cell and can become any tissue in the body.

The study provides a direct and unexpected molecular link between cancer and stem cell science through retinoblastoma, or Rb, one of the best known of a class of proteins called tumor suppressors. Although Rb has long been known to control the rate of cell division, the researchers found that it also directly binds and inhibits the expression of genes involved in pluripotency.

"We were very surprised to see that retinoblastoma directly connects control of the cell cycle with pluripotency," said Julien Sage, PhD, associate professor of pediatrics and of genetics. "This is a completely new idea as to how retinoblastoma functions. It physically prevents the reacquisition of stem cellness and pluripotency by inhibiting gene expression."

Marius Wernig, MD, associate professor of pathology, said, "The loss of Rb appears to directly change a cell's identity. Without the protein, the cell is much more developmentally fluid and is easier to reprogram into an iPS cell."

Wernig and Sage, both members of the Stanford Cancer Institute, share senior authorship of the study, which will be published online Nov. 13 in Cell Stem Cell. Postdoctoral scholar Michael Kareta, PhD, is the lead author.

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Tumor suppressor also inhibits key property of stem cells, Stanford researchers say

UCLA Researchers Identify Unique Protein Key to the Development of Blood Stem Cells

By adminNovember 13, 2014Uncategorized

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Newswise Led by Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research member Dr. Hanna Mikkola, UCLA scientists have discovered a unique protein that is integral to the self-renewal of hematopoietic stem cells (HSCs) during human development.

This discovery lays the groundwork for researchers to generate HSCs in the lab (in vitro) that better mirror those that develop in their natural environment (in vivo). This could lead to improved therapies for blood-related diseases and cancers by enabling the creation of patient-specific blood stem cells for transplantation.

The findings are reported online November 13, 2014, ahead of print in the journal Cell Stem Cell.

The research community has long sought to harness the promise of pluripotent stem cells (PSCs) to overcome a significant roadblock in making cell-based therapies blood and immune diseases more broadly available, which has been hampered by the inability to generate and expand human HSCs in culture. HSCs are the blood forming cells that serve as the critical link between PSCs and fully differentiated cells of the blood system. The ability of HSCs to self-renew (replicate themselves) and differentiate to all blood cell types, is determined in part by the environment that the stem cell came from, called the niche.

In the five-year study, Mikkola and Drs. Sacha Prashad and Vincenzo Calvanese, members of Mikkolas lab and lead authors of the study, investigated a unique HSC surface protein called GPI-80. They found that it was produced by a specific subpopulation of human fetal hematopoietic cells that were the only group that could self-renew and differentiate into various blood cell types. They also found that this subpopulation of hematopoietic cells was the sole population able to permanently integrate into and thrive within the blood system of a recipient mouse.

Mikkola and colleagues further discovered that GPI-80 identifies HSCs during multiple phases of human HSC development and migration. These include the early first trimester of fetal development when newly generated HSCs can be found in the placenta, and the second trimester when HSCs are actively replicating in the fetal liver and the fetal bone marrow.

We found that whatever HSC niche we investigated, we could use GPI-80 as the best determinant to find the stem cell as it was being generated or colonized different hematopoietic tissues, said Mikkola, associate professor of molecular, cell and development biology at UCLA and also a member of the Jonsson Comprehensive Cancer Center. Moreover, loss of GPI-80 caused the stem cells to differentiate. This essentially tells us that GPI-80 must be present to make HSCs. We now have a very unique marker for investigating how human hematopoietic cells develop, migrate and function.

Mikkolas team is actively exploring different stages of human HSC development and PSC differentiation based on the GPI-80 marker, and comparing how blood stem cells are being generated in vitro and in vivo. This paves the way for scientists to redirect PSCs into patient-specific HSCs for transplantation into the patient without the need to find a suitable donor.

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UCLA Researchers Identify Unique Protein Key to the Development of Blood Stem Cells

Rafael Nadal to Receive Stem Cell Treatment for Back Pain – TOI – Video

By adminNovember 13, 2014Stem Cell Treatment

Rafael Nadal to Receive Stem Cell Treatment for Back Pain - TOI
Rafael Nadal to Receive Stem Cell Treatment for Back Pain Rafael Nadal #39;s doctor says the 14-time Grand Slam winner will receive stem cell treatment on his ai...

By: The Times of India

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Rafael Nadal to Receive Stem Cell Treatment for Back Pain - TOI - Video

Researchers Discover Breakthrough Stem Cell Treatment For Parkinson's Disease

By adminNovember 13, 2014Stem Cell Treatment

By C. Rajan, contributing writer

Researchers at Lund University in Sweden have made a major breakthrough in Parkinson's disease treatment by developing stem cell-derived brain cells that can replace the cells lost due to the disease, thus paving the way for the first stem cell transplant treatment for Parkinsons patients.

Parkinson's disease, which affects about 10 million people worldwide, is a degenerative nervous system condition which causes tremors, muscle weakness, stiffness, and loss in mobility. Parkinson's is caused by loss of dopamine-producing neurons in the brain. Dopamine is an essential neurotransmitter that is required for regulating movement and emotions.

In this study, for the first time ever, the researchers were able to convert human embryonic stem cells into dopamine producing neurons, which behaved like native dopamine cells lost in the disease.

The study was led by Malin Parmar, associate professor in Lund's Department of Medicine, and conducted at both Lund University and at MIRCen in Paris as part of the EU networks NeuroStemCell and NeuroStemcellRepair.

According to Medical News Today, the researchers produced rat models of Parkinson's disease by destroying the dopamine cells in one part of the rat's brain, and then they transplanted the new dopamine producing stem cell neurons. These next generation dopamine neurons were found to survive long term, restore the lost dopamine, and form long distance connections to the correct parts of the brain when transplanted into rats. Most excitingly, these transplanted stem cells reversed the damage from the disease.

As the new dopamine neurons have the same properties and functions of native cells lost in Parkinson's disease and can be produced in unlimited quantities from stem cell lines, this treatment shows promise in moving into clinical applications as stem cell transplants for Parkinsons.

"This study shows that we can now produce fully functioning dopamine neurons from stem cells. These cells have the same ability as the brains normal dopamine cells to not only reach but also to connect to their target area over longer distances. This has been our goal for some time, and the next step is to produce the same cells under the necessary regulations for human use. Our hope is that they are ready for clinical studies in about three years", says Malin Parmar.

Human embryonic stem cells (ESC) are powerful treatment options due to their ability to change into any cell type in the body. However, it is difficult to get them to change into the desired cell types, and research efforts are also hampered due to the ethical concerns associated with embryonic stem cells.

The study is published in the journal,Cell Stem Cell, titled Human ESC-Derived Dopamine Neurons Show Similar Preclinical Efficacy and Potency to Fetal Neurons when Grafted in a Rat Model of Parkinsons Disease.

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Researchers Discover Breakthrough Stem Cell Treatment For Parkinson's Disease

Ilfords Fathima Hilmy finds possible stem cell match in Brazil

By adminNovember 12, 2014Stem Cell Doctors

12:44 11 November 2014

Harry Kemble

Fathima Hilmy, of High Road, Ilford.

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A 25-year-old teaching assistant may have had her international appeal for a stem cell donor answered.

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Sri Lankan Fathima Hilmy, of High Road, Ilford - known as Fathima Nusla by her community - has been told by doctors she has an 80 per cent chance of a successful match after a potential donor was found in Brazil.

The unnamed donor will now be medically tested to see if they can undergo the intensive and challenging procedure.

Fathima, 25, has been in and out of hospital after being originally diagnosed with acute myeloid leukaemia in 2012.

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Ilfords Fathima Hilmy finds possible stem cell match in Brazil

Toughest for Tamil Nadu patients to get donor stem cells

By adminNovember 12, 2014Stem Cell Medicine

CHENNAI: It is harder for natives of Tamil Nadu to find a matching donor for a stem cell transplant compared to other states in the country. The suspected villain: Their genes.

A study published recently in British medical journal 'The Lancet' found that the likelihood of finding a matching stem cell donor for patients with blood-related problems in Tamil Nadu is 44.2% provided the registry had 10 lakh donors. The situation is the opposite in Haryana, with people in that state having the best chances (81.2%) of finding a donor.

Experts say consanguineous marriages are to blame. Consanguineous marriages increase the chances of patients finding a match within their small community but limit the possibility of finding one from a general donor pool.

"Unlike in other countries, stem cell variation in India is complex and dependent on ethnic variation," said Dr Dolly Daniel, professor of the department of transfusion medicine at Christian Medical College, Vellore, who was party of the study team. "Our aim was to find the size and genetic composition of each region and its impact on the proportion of patients who will be able to ?nd a suitable match."

She said Tamil Nadu could be at the tail-end of the list of states they surveyed because of inbreeding and a limited number of donors.

Stem cells are used to regenerate and repair diseased or damaged tissues. Adult stem cells are drawn from bone marrow, blood and the umbilical cord and are used to treat blood-related ailments like leukemia, thalassemia and as well as immunodeficiency.

The possibility of finding a matching stem cell donor within the family is around 30%.

"Finding a matching stem cell donor for the remaining 70% is a complex process. Most seek a graft from registries of unrelated adult donors or banked umbilical cord blood units," said Dr P Srinivasan, co-founder and chairman of Jeevan Stem Cell Bank.

Although the India stem cell industry is estimated to touch $540 million (Rs 3,250 crore) by 2015, the study noted that in terms of the number of donors, India has lagged in meeting demand. The study surveyed 10 adult donor and umbilical cord bank registries and clinical transplant centres in India and studied stem cells of 26 239 individuals.

The possibility of finding a perfect match within India is an average of 14.4% for a registry size of 25,000 and touches 60.6% for a size of 10 lakh. Registries in the country currently have around 1 lakh donors. The study said only when Indian registries have more than 2 lakh donors would patients have a good chance of finding the right match.

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Toughest for Tamil Nadu patients to get donor stem cells

STEM CELL FINDING WELL-NOTED IN LA JOLLA STEM CELL FINDING SHOWS PROMISE

By adminNovember 12, 2014Uncategorized

By Bradley J. Fikes U-T5:05 a.m.Nov. 12, 2014

A rat model of Parkinsons disease has been successfully treated with neurons derived from human embryonic stem cells, according to a new study led by Swedish scientists.

Its a promising sign for scientists at The Scripps Research Institute and Scripps Health who hope to perform similar therapy on Parkinsons patients using artificial embryonic stem cells.

In rats and people, neurons that make the neurotransmitter dopamine are essential for normal movement. Parkinsons destroys those cells, leading to the movement difficulties that characterize the disease.

Researchers transplanted dopamine-producing cells grown from human embryonic stem cells into the brains of rats whose own dopamine-making neurons had been destroyed. Within five months, the transplanted cells boosted dopamine production to normal levels, restoring normal movement in the rats.

The study was published Thursday in the journal Cell Stem Cell. The senior author was Malin Parmar of Lund University in Sweden.

The results support the Scripps approach of using artificial embryonic stem cells called induced pluripotent stem cells, or IPS cells said Jeanne Loring, head of the Center for Regenerative Medicine at Scripps Research. Loring and the Scripps Health network are part of a group called Summit 4 Stem Cell thats raising funds to treat eight Parkinsons patients with their own IPS cells.

Particularly significant is the studys comparison of the effects of dopamine-making neurons derived from fetal cells to those of embryonic stem cells, Loring said by email.

In the 1980s and 1990s, there were several clinical trials that showed that grafts of fetal brain containing the precursors of dopamine neurons could reverse the effects of Parkinsons disease in some patients, Loring said. We and the others developing stem cell therapies based our plans on the results of those studies, but no one had ever directly compared fetal tissue and human pluripotent stem cell-derived dopamine neurons in an animal model of (Parkinsons).

Induced pluripotent stem cells appear to have much the same capacity as human embryonic stem cells to generate different tissues and organs.

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STEM CELL FINDING WELL-NOTED IN LA JOLLA STEM CELL FINDING SHOWS PROMISE

STEM CELL FINDING WELL-NOTED IN LA JOLLA

By adminNovember 12, 2014Uncategorized

By Bradley J. Fikes U-T5:08 a.m.Nov. 12, 2014

A rat model of Parkinsons disease has been successfully treated with neurons derived from human embryonic stem cells, according to a new study led by Swedish scientists.

Its a promising sign for scientists at The Scripps Research Institute and Scripps Health who hope to perform similar therapy on Parkinsons patients using artificial embryonic stem cells.

The study was published Thursday in the journal Cell Stem Cell. The senior author was Malin Parmar of Lund University in Sweden.

Loring and the Scripps Health network are part of a group called Summit 4 Stem Cell thats raising funds to treat eight Parkinsons patients with their own IPS cells.

Particularly significant is the studys comparison of the effects of dopamine-making neurons derived from fetal cells to those of embryonic stem cells, Loring said by email.

Study Identifying Cell of Origin for Large, Disfiguring Nerve Tumors Lays Groundwork for Development of New Therapies

By adminNovember 11, 2014Stem Cell Medical Center

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Newswise DALLAS November 11, 2014 UTSouthwestern Medical Center researchers have determined the specific type of cell that gives rise to large, disfiguring tumors called plexiform neurofibromas, a finding that could lead to new therapies for preventing growth of these tumors.

This advance provides new insight into the steps that lead to tumor development and suggests ways to develop therapies to prevent neurofibroma formation where none exist today, said Dr. Lu Le, Assistant Professor of Dermatology at UTSouthwestern and senior author of the study, published online and in Cancer Cell.

Plexiform neurofibromas, which are complex tumors that form around nerves, occur in patients with a genetic disorder called neurofibromatosis type 1 (NF1), which affects 1 in 3,500 people. About 30 percent of NF1 patients develop this type of tumor, which is typically benign.

NF1 patients with plexiform neurofibromas, however, have a 10 percent lifetime risk of the tumors developing into malignant peripheral nerve sheath tumors (MPNSTs), a deadly, incurable type of soft-tissue cancer. In addition, due to their unusual capacity for growth, plexiform neurofibromas can be life-threatening by their physical impairment of vital organs or neural function.

While there are no currently approved therapies for either MPNSTs or plexiform neurofibromas, Dr. Le said determining the cell type and location from which these tumors originate is an important step toward discovering new drugs that inhibit tumor development.

If we can isolate and grow the cells of origin for neurofibromas, then we can reconstruct the biological steps that lead these original cells to tumor stage, said Dr. Le, a member of the Harold C. Simmons Cancer Center. Once we know the critical steps in the process, then we can design inhibitors to block each step in an effort to prevent or slow tumor formation.

Using a process called genetic labeling for cell fate tracing, researchers determined that plexiform neurofibromas originate from Schwann cell precursors in embryonic nerve roots.

This study addresses a fundamental question in the neurofibromatosis field, Dr. Le said. It points to the importance of stem cells and their immediate progenitors in the initiation of tumors, consistent with the notion that these neoplasms originate in a subset of primitive precursors and that most cells in an organ do not generate tumors.

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