Washington, May 5 : Researchers have for the first time identified the molecular cause of fibroid uterine tumors, which affect millions of women causing irregular bleeding, anemia, pain and infertility.

Despite the high prevalence of the tumors, which occur in 60 percent of women by age 45, the molecular trigger has been unknown.

Now, a new Northwestern Medicine preclinical research has identified a single stem cell that develops a mutation, starts to grow uncontrollably and activates other cells to join its frenzied expansion, as the key player of the disease.

'It loses its way and goes wild,' said Serdar Bulun, M.D., the chair of obstetrics and gynecology at Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital.

'No one knew how these came about before. The stem cells make up only 1 and a half percent of the cells in the tumor, yet they are the essential drivers of its growth,' he explained.

The stem cell initiating the tumor carries a mutation called MED12. Recently, mutations in the MED12 gene have been reported in the majority of uterine fibroid tissues. Once the mutation kicks off the abnormal expansion, the tumors grow in response to steroid hormones, particularly progesterone.

For the study, researchers examined the behaviour of human fibroid stem cells when grafted into a mouse, a novel model initiated by Northwestern scientist Takeshi Kurita, a research associate professor of obstetrics and gynecology.

The most important characteristic of fibroid stem cells is their ability to generate tumors. Tumors originating from the fibroid stem cell population grew 10 times larger compared to tumors initiated with the main cell population, suggesting a key role of these tumor stem cells is to initiate and sustain tumor growth.

'Understanding how this mutation directs the tumor growth gives us a new direction to develop therapies,' said Bulun, also the George H. Gardner Professor of Clinical Gynecology.

The paper has been published in the journal PLoS ONE. (ANI)

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Stem cell mutation triggers fibroid tumors

Public release date: 4-May-2012 [ | E-mail | Share ]

Contact: Kim Irwin kirwin@mednet.ucla.edu 310-206-2805 University of California - Los Angeles Health Sciences

In an effort to identify the underlying causes of neurological disorders that impair motor functions such as walking and breathing, UCLA researchers have developed a novel system to measure the communication between stem cell-derived motor neurons and muscle cells in a Petri dish.

The study provides an important proof of principle that functional motor circuits can be created outside of the body using stem cell-derived neurons and muscle cells, and that the level of communication, or synaptic activity, between the cells could be accurately measured by stimulating motor neurons with an electrode and then measuring the transfer of electrical activity into the muscle cells to which the motor neurons are connected.

When motor neurons are stimulated, they release neurotransmitters that depolarize the membranes of muscle cells, allowing the entry of calcium and other ions that cause them to contract. By measuring the strength of this activity, one can get a good estimation of the overall health of motor neurons. That estimation could shed light on a variety of neurodegenerative diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis, or Lou Gehrig's disease, in which the communication between motor neurons and muscle cells is thought to unravel, said study senior author Bennett G. Novitch, an assistant professor of neurobiology and a scientist with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

The findings of the study appear May 4, 2012 in PLoS ONE, a peer-reviewed journal of the Public Library of Science.

"Now that we have this method to measure the strength of the communications between motor neurons and muscle cells, we may be able to begin exploring what happens in the earliest stages of motor neuron disease, before neuronal death becomes prevalent," Novitch said. "This can help us to pinpoint where things begin to go wrong and provide us with new clues into therapeutic interventions that could improve synaptic communication and promote neuronal survival."

Novitch said the synaptic communication activity his team was able to create and measure using mouse embryonic stem cell-derived motor neurons and muscle cells looks very similar what is seen in a mouse, validating that their model is a realistic representation of what is happening in a living organism.

"That gives us a good starting point to try to model what happens in cells that harbor genetic mutations that are associated with neurodegenerative diseases,. To do that, we had to first define an activity profile of normal synaptic communication," he said. "Some research suggests that a breakdown in this communication can be an early indication of disease progression or possibly an initiating event. Neurons that cannot effectively transmit information to muscle cells will eventually withdraw their contacts, causing both the neurons and muscle cells to degenerate over time. Hopefully, we can now create disease models that will allow us to study what is happening."

In this study, Novitch and his team, led by Joy Umbach, an associate professor of molecular and medical pharmacology, used mouse embryonic stem cells to create the motor neurons and previously established lines of muscle precursors to produce muscle fibers. They put both cells together in a Petri dish, and the cells were cultured in such a way to encourage communication. Novitch said the team wanted to see if they would naturally form synaptic contacts and whether or not there was neural transmission between them.

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UCLA scientists measure communication between stem cell-derived motor neurons and muscle cells

MIAMI--(BUSINESS WIRE)--

The University of Miami Miller School of Medicines Interdisciplinary Stem Cell Institute (ISCI) today announced that it received a $10 million grant from The Starr Foundation, one of the largest private foundations in the United States. The grant will support ISCI in broadening its preclinical and clinical research on stem cells, and help accelerate its pipeline of translational research and programs for a wide range of debilitating conditions including cardiac disease, cancer, wound healing, stroke, glaucoma and chronic kidney and gastrointestinal diseases.

This is a momentous and transformative gift for the Interdisciplinary Stem Cell Institute, said Joshua M. Hare, M.D., F.A.C.C., F.A.H.A., Louis Lemberg Professor of Medicine at the University of Miami Miller School of Medicine and director of ISCI. We are so gratified that the level of science being conducted here was recognized by this very generous grant from The Starr Foundation. With this award, we join the ranks of the other major top-tier universities funded by The Starr Foundation. This support, along with our growing NIH funding, technology transfer, and other philanthropic efforts guarantees the stability of ISCI through the end of the decade, and will allow us to continue to push the boundaries of regenerative medicine with the goal of improving human health.

Stem cells and regenerative medicine are poised to transform the way we practice medicine, cure disease and treat injuries. To realize this potential, the University of Miami Miller School of Medicine is performing world-leading research at ISCI, said Pascal J. Goldschmidt, M.D., Senior Vice President for Medical Affairs and Dean of the Miller School of Medicine, and Chief Executive Officer of the University of Miami Health System. We are extremely proud of this recognition by The Starr Foundation that ISCI, and the Miller School of Medicine, are leading the way for stem cell and regenerative medicine breakthroughs.

Donna E. Shalala, President of the University of Miami, said the grant from the foundation will have long-reaching implications for future medicine. The team at ISCI is making new discoveries on a number of fronts and this substantial support from The Starr Foundation propels that work forward, both in the laboratory and in clinical trials.

For more on the grant, click here.

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University of Miami’s Interdisciplinary Stem Cell Institute Awarded $10 Million Grant from Starr Foundation

MIAMI--(BUSINESS WIRE)--

The University of Miami Miller School of Medicines Interdisciplinary Stem Cell Institute (ISCI) today announced that it received a $10 million grant from The Starr Foundation, one of the largest private foundations in the United States. The grant will support ISCI in broadening its preclinical and clinical research on stem cells, and help accelerate its pipeline of translational research and programs for a wide range of debilitating conditions including cardiac disease, cancer, wound healing, stroke, glaucoma and chronic kidney and gastrointestinal diseases.

This is a momentous and transformative gift for the Interdisciplinary Stem Cell Institute, said Joshua M. Hare, M.D., F.A.C.C., F.A.H.A., Louis Lemberg Professor of Medicine at the University of Miami Miller School of Medicine and director of ISCI. We are so gratified that the level of science being conducted here was recognized by this very generous grant from The Starr Foundation. With this award, we join the ranks of the other major top-tier universities funded by The Starr Foundation. This support, along with our growing NIH funding, technology transfer, and other philanthropic efforts guarantees the stability of ISCI through the end of the decade, and will allow us to continue to push the boundaries of regenerative medicine with the goal of improving human health.

Stem cells and regenerative medicine are poised to transform the way we practice medicine, cure disease and treat injuries. To realize this potential, the University of Miami Miller School of Medicine is performing world-leading research at ISCI, said Pascal J. Goldschmidt, M.D., Senior Vice President for Medical Affairs and Dean of the Miller School of Medicine, and Chief Executive Officer of the University of Miami Health System. We are extremely proud of this recognition by The Starr Foundation that ISCI, and the Miller School of Medicine, are leading the way for stem cell and regenerative medicine breakthroughs.

Donna E. Shalala, President of the University of Miami, said the grant from the foundation will have long-reaching implications for future medicine. The team at ISCI is making new discoveries on a number of fronts and this substantial support from The Starr Foundation propels that work forward, both in the laboratory and in clinical trials.

For more on the grant, click here.

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University of Miami’s Interdisciplinary Stem Cell Institute Awarded $10 Million Grant from Starr Foundation

EXTON, Pa.--(BUSINESS WIRE)--

In collaboration with Fibrocell Science, Inc., (OTCBB:FCSC.OB), researchers at the University of California, Los Angeles (UCLA) have identified two rare adult stem cell-like subpopulations in adult human skin, a discovery that may yield further ground-breaking research in the field of personalized medicine for a broad range of diseases. Using technology developed by Fibrocell Science, Inc. the researchers were able to confirm the existence of these two types of cells in human skin cell cultures, potentially providing a source of stem cell-like subpopulations from skin biopsies, which are quicker to perform, relatively painless and less invasive than bone marrow and adipose tissue extractions, which are the current methods for deriving adult stem cells for patient-specific cellular therapies.

The findings, which are reported in the inaugural issue of BioResearch Open Access, pertain to two subtypes of cells: SSEA3-expressing regeneration-associated (SERA) cells, which may play a role in the regeneration of human skin in response to injury and mesenchymal adult stem cells (MSCs), which are under investigation (by many independent researchers) for their ability to differentiate into the three main types of cells: osteoblasts (bone cells), chondrocytes (cartilage cells) and adipocytes (fat cells). Finding these specialized cells within the skin cell cultures is important because rather than undergoing a surgical organ or tissue transplantation to replace diseased or destroyed tissue, patients may one day be able to benefit from procedures by which stem cells are extracted from their skin, reprogrammed to differentiate into specific cell types and reimplanted into their bodies to exert a therapeutic effect. Research in this area is ongoing.

Finding these rare adult stem cell-like subpopulations in human skin is an exciting discovery and provides the first step towards purifying and expanding these cells to clinically relevant numbers for application to a variety of potential personalized cellular therapies for osteoarthritis, bone loss, injury and/or damage to human skin as well as many other diseases, said James A. Byrne, Ph.D., the studys lead author and Assistant Professor of Molecular and Medical Pharmacology at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. In addition to pursuing our own research investigations with Fibrocell Science using this method, we envision a time not too far in the future when we will be able to isolate and produce mesenchymal stem cells and SERA cells on demand from skin samples, which may allow other researchers in need of specialized cells to pursue their own lines of medical and scientific research.

We congratulate the UCLA researchers on the publication of their breakthrough data, which may ultimately lead to new patient-specific, personalized cellular therapies to treat various diseases, said David Pernock, Chairman and CEO of Fibrocell Science, Inc. Fibrocell Science is proud of our role in helping to establish the potential of dermal skin cells for the future of personalized, regenerative medicine. We look forward to continuing our relationship with UCLA and Dr. Byrnes team to advance this research.

Discovering Viable, Regenerative Cells in the Skin

Dr. Byrne and colleagues confirmed previous research identifying a rare population of cells in adult human skin that has a marker called the stage-specific embryonic antigen 3 (SSEA3). Dr. Byrne observed that there was a significant increase in the number of SSEA3 expressing cells following injury to human skin, supporting the hypothesis that the SSEA3 biomarker can be used to facilitate the identification and isolation of these cells with tissue-regenerative properties.

Using Fibrocells proprietary technology, the researchers collected cells from small skin samples, cultured the cells in the lab, and purified them via a technique known as fluorescence-activated cell sorting (FACS). Under FACS, cells in suspension were tagged with fluorescent markers specific for undifferentiated stem cells. This method allowed the researchers to separate the rare cell subpopulations from other types of cells.

Dr. Byrne and colleagues also observed a rare subpopulation of functional MSCs in human skin that existed in addition to the SERA cells.

Being able to identify two sub-populations of rare, viable and functional cells that behave like stem cells from within the skin is an important finding because both cell types have the potential to be investigated for diverse clinical applications, said Dr. Byrne.

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Fibrocell Science Technology Leads to Discovery of Two Rare Adult Stem Cell-Like Subpopulations in Human Skin

PHILADELPHIA HIV patients treated with genetically modified T cells remain healthy up to 11 years after initial therapy, researchers from the Perelman School of Medicine at the University of Pennsylvania report in the new issue of Science Translational Medicine. The results provide a framework for the use of this type of gene therapy as a powerful weapon in the treatment of HIV, cancer, and a wide variety of other diseases.

"We have 43 patients and they are all healthy," says senior author Carl June, MD, a professor of Pathology and Laboratory Medicine at Penn Medicine. "And out of those, 41 patients show long term persistence of the modified T cells in their bodies."

Early gene therapy studies raised concern that gene transfer to cells via retroviruses might lead to leukemia in a substantial proportion of patients, due to mutations that may arise in genes when new DNA is inserted. The new long-term data, however, allay that concern in T cells, further buoying the hope generated by work June's team published in 2011 showing the eradication of tumors in patients with chronic lymphocytic leukemia using a similar strategy.

"If you have a safe way to modify cells in patients with HIV, you can potentially develop curative approaches," June says. "Patients now have to take medicine for their whole lives to keep their virus under control, but there are a number of gene therapy approaches that might be curative." A lifetime of anti-HIV drug therapy, by contrast, is expensive and can be accompanied by significant side effects.

They also note that the approach the Penn Medicine team studied may allow patients with cancers and other diseases to avoid the complications and mortality risks associated with more conventional treatments, since patients treated with the modified T cells did not require drugs to weaken their own immune systems in order for the modified cells to proliferate in their bodies after infusion, as is customary for cancer patients who receive stem cell transplants.

To demonstrate the long-term safety of genetically modified T cells, June and colleagues have followed HIV-positive patients who enrolled in three trials between 1998 and 2002. Each patient received one or more infusions of their own T cells that had been genetically modified in the laboratory using a retroviral vector. The vector encoded a chimeric antigen receptor that recognizes the HIV envelope protein and directs the modified T cell to kill any HIV-infected cells it encounters.

As is standard for any trial, the researchers carefully monitored patients for any serious adverse events immediately after infusion -- none of which were seen. Additionally, because of the earlier concerns about long-term side effects, the U.S. Food and Drug Administration also asked the team to follow the patients for up to 15 years to ensure that the modified T cells were not causing blood cancers or other late effects. Therefore, each patient underwent an exam and provided blood samples during each of the subsequent years.

Now, with more than 500 years of combined patient safety data, June and colleagues are confident that the retroviral vector system is safe for modifying T cells. By contrast, June notes, the earlier, worrying side effects were seen when viral vectors were used to modify blood stem cells. The new results show that the target cell for gene modification plays an important role in long-term safety for patients treated. "T cells appear to be a safe haven for gene modification," June says.

The multi-year blood samples also show that the gene-modified T cell population persists in the patients' blood for more than a decade. In fact, models suggest that more than half of the T cells or their progeny are still alive 16 years after infusion, which means one treatment might be able to kill off HIV-infected cells for decades. The prolonged safety data means that it might be possible to test T cell-based gene therapy for the treatment of non-life threatening diseases, like arthritis.

"Until now, we've focused on cancer and HIV-infection, but these data provide a rationale for starting to focus on other disease types," June says. "What we have demonstrated in this study and recent studies is that gene transfer to T cells can endow these cells with enhanced and novel functions. We view this as a personalized medicine platform to target disease using a patient's own cells."

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Genetically Modified T Cell Therapy Shown to be Safe, Lasting in Decade-Long Penn Medicine Study of HIV Patients