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Joslin Scientists Create the First IPS Cells to Offer Human Model of Insulin Resistance

Posted: July 25, 2014 at 4:52 am

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Newswise BOSTON July 24, 2014 Japanese biologist Shinya Yamanaka won a Nobel Prize in 2012 for discovering how to create induced pluripotent stem cells (iPSCs), cells derived from normal adult cells that have the ability to differentiate into almost any other kind of cells. Scientists at Joslin Diabetes Center now have created the first iPSCs that offer a human model of insulin resistance, a key driver of type 2 diabetes.

This is one of the very first studies of human iPSC models for type 2 diabetes, and it points out the power of this technology to look at the nature of diabetes, which is complex and may be different in different individuals, says C. Ronald Kahn, MD, Joslins Chief Academic Officer and the Mary K. Iacocca Professor of Medicine at Harvard Medical School.

Until now, scientists examining the causes and effects of insulin resistance have struggled with a general lack of human cell lines from tissues such as muscle, fat and liver that respond significantly to insulin, Kahn says. Studying insulin resistance as it progresses through pre-clinical stages of type 2 diabetes has been particularly challenging.

There have been no good human cell models to study insulin resistance, but such cells can now be made with iPSCs, says Kahn, co-senior author on a paper about the study published in the journal Diabetes.

Generation of iPSCs typically starts with fibroblasts (connective tissue cells) from skin samples. Kahn and his colleagues used fibroblasts from three patients with severe insulin resistance brought on by mutations in the gene for the insulin receptor (IR)a molecule that crosses the cell membrane and plays a key role in insulin signaling and glucose metabolism.

The Joslin researchers reprogrammed the fibroblasts into iPSCs by using viral procedures that activated four genes that together maintain cells in the iPSC state. The scientists then looked at gene activation in insulin signaling pathways for iPSCs and fibroblasts with IR mutations, and for corresponding cells derived from people without those mutations.

Among the study findings, IR mutations alter expression of many genes both in fibroblasts and iPSCs compared to normal cells, but the impact is very much dependent on the cell type, says Kahn. You see one type of expression pattern in the fibroblasts and a different type of pattern in the iPSCs.

Insulin is a key ingredient for the growth and proliferation of normal stem cells, and the study demonstrated that insulin resistance also reduces the ability of the iPSCs to grow and proliferate. That defect may represent a previously unrecognized mechanism that aids in developing diabetes, Kahn says, as well as helping to explain the problems in wound healing, tissue repair and even beta-cell growth that are common among people with diabetes.

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Tissue Collection Aids Search for Neurologic and Neuromuscular Disease Causes and Cures

Posted: July 25, 2014 at 4:50 am

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Newswise LOS ANGELES (July 24, 2014) Like other major research centers studying genetic causes of uncommon and poorly understood nervous system disorders, Cedars-Sinai maintains a growing collection of DNA and tissue samples donated by patients.

What sets Cedars-Sinais Repository of Neurologic and Neuromuscular Disorders apart is its special emphasis on tissue collection part of its focus on creating future individualized treatments for patients.

One of our major priorities is to advance the concept of personalized medicine. The idea is to take DNA from a patient, look at the cells derived from their tissue, and try to understand why this particular person got this disease. Then we can determine which therapy or therapies would work for each individual by first testing their cells. Many centers look at the genetics; ours is dedicated to looking at the genetics and the patients tissues, combining the two to understand how to treat the disease, said Robert H. Baloh, MD, PhD, director of neuromuscular medicine in the Department of Neurology and director of the ALS Program for research and treatment of amyotrophic lateral sclerosis, or Lou Gehrigs disease.

This individualized treatment approach depends on collaborative efforts among doctors and researchers who treat and study individual diseases and scientists at the Cedars-Sinai Regenerative Medicine Institute, one of a very few hospital-based centers devoted to stem cell research. The teams work together to discover disease-generating molecular and cellular defects, make disease-in-a-dish models and begin to fashion personalized stem cell-based research interventions.

We know that nearly every disease has some genetic component some more than others so we collect DNA for research to identify those genetic elements. But weve also expanded our focus to include the collection of skin and blood samples that can be turned into specialized stem cells. Patients are usually very willing to donate tissue to try and help us understand the causes of their neurologic or neuromuscular disease, said Baloh, a member of the Brain Program at the Regenerative Medicine Institute.

Baloh and colleagues recently showed this approach is feasible, using skin biopsies from patients with ALS. With induced pluripotent stem cells, or iPSCs, they created ALS neurons in a lab dish. Then, inserting molecules made of small stretches of genetic material, they blocked the damaging effects of a defective gene. This provided proof of concept for a new therapeutic strategy an important step in moving research findings into clinical trials.

Baloh, the repositorys principal investigator, has a particular interest in ALS and other neuromuscular disorders, but DNA, tissue and data collection is conducted for Cedars-Sinai neuroscience researchers studying virtually any disease. And its holdings can have widespread influence: Repositories of genetic material enable scientists studying similar diseases at multiple research centers to access patient data in larger quantities than any single site could provide.

We work with many other research institutions across the country to share the samples themselves as well as de-identified information about the patients what disease they have, the severity of their disease, and similar disorder-related details. This improves our ability to find new gene abnormalities, because it cant always be done with just tens or even hundreds of patients. We may need thousands of patients, especially for very rare genetic forms of disease that have very subtle genetic effects. Therefore, we study our own patients in great detail, but we also share our resources more broadly, said Baloh, adding that genetic discoveries often have implications even for patients who dont have genetic forms of disease.

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Experiments prove 'stemness' of individual immune memory cells

Posted: July 25, 2014 at 4:47 am

PUBLIC RELEASE DATE:

24-Jul-2014

Contact: Vera Siegler vera.siegler@tum.de 49-892-892-2731 Technische Universitaet Muenchen

This news release is available in German.

The immune system has evolved to recognize and respond to threats to health, and to provide life-long memory that prevents recurrent disease. A detailed understanding of the mechanism underlying immunologic memory, however, has remained elusive. Since 2001, various lines of research have converged to support the hypothesis that the persistence of immune memory arises from a reservoir of immune cells with stem-cell-like potential. Until now, there was no conclusive evidence, largely because experiments could only be carried out on populations of cells. This first strict test of the stem cell hypothesis of immune memory was based on mapping the fates of individual T cells and their descendants over several generations.

That experimental capability was developed through a long-term collaboration, focused on clinical cell processing and purification, between researchers based in Munich and Seattle. Since 2009, the groups of Prof. Dirk Busch at the Technische Universitt Mnchen (TUM) and Prof. Stanley Riddell at the Fred Hutchinson Cancer Research Center have combined their technological and clinical expertise under the auspices of the TUM Institute for Advanced Study. The University of Heidelberg, the University of Dsseldorf, the Helmholtz Center Munich, the German Cancer Research Center (DKFZ), and the National Center for Infection Research (DZIF) also contributed to the present study.

Homing In On The "Stemness" of T Cells

After generating an immune response in laboratory animals, TUM researchers Patricia Graef and Veit Buchholz separated complex "killer" T cell populations enlisted to fight the immediate or recurring infection. Within these cell populations, they then identified subgroups and proceeded with a series of single-cell adoptive transfer experiments, in which the aftermath of immune responses could be analyzed in detail. Here the ability to identify and characterize the descendants of individual T cells through several generations was crucial.

The researchers first established that a high potential for expansion and differentiation in a defined subpopulation, called "central memory T cells," does not depend exclusively on any special source such as bone marrow, lymph nodes, or spleen. This supported but did not yet prove the idea that certain central memory T cells are, effectively, adult stem cells. Further experiments, using and comparing both memory T cells and so-called naive T cells that is, mature immune cells that have not yet encountered their antigen enabled the scientists to home in on stem-cell-like characteristics and eliminate other possible explanations.

Step by step, the results strengthened the case that the persistence of immune memory depends on the "stemness" of the subpopulation of T cells termed central memory T cells: Individual central memory T cells proved to be "multipotent," meaning that they can generate diverse types of offspring to fight an infection and to remember the antagonist. Further, these individual T cells self-renew into secondary memory T cells that are, again, multipotent at the single-cell level. And finally, individual descendants of secondary memory T cells are capable of fully restoring the capacity for a normal immune response.

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Stem cell agency tightens ethics rules

Posted: July 25, 2014 at 4:45 am

Stem cell agency President C. Randal Mills (left) and Chairman of the Board Jonathan Thomas.

Responding to his predecessor's ethically controversial departure, the president and chief executive of California's stem cell agency said Thursday he is taking legal steps to minimize conflicts of interests with those who have business before the agency.

C. Randal Mills said he will not take a job with any company funded by the California Institute for Regenerative Medicine for one year after he departs the agency. In addition, he also will not accept gifts or travel payments from any company, institution or person who gets agency funding.

Mills' action, announced at the agency's meeting in Millbrae, will be enforced with a legal agreement he will sign. His action comes less than a month after he replaced Alan Trounson as the agency chief. One week after his departure, CIRM-funded StemCells Inc. announced it had appointed Trounson to its board. StemCells Inc. had received an award of nearly $20 million from the agency to develop a therapy for Alzheimers disease.

While Trounson's appointment wasn't illegal, critics said it was unseemly for him to join a company that had received agency funding so soon after he left CIRM. An ethical controversy could harm the agency's chances of getting more funding from California voters, who gave the agency $3 billion with the passage of Proposition 71 in 2004.

Mills said the new rules apply only to himself, because of his central role at CIRM.

"This specifically addresses an issue where an individual in an organization has a disproportionate amount of power, and I want to make sure it's known that power will not be abused," Mills said.

Mills made the right decision, said Jeanne Loring, a CIRM-funded stem cell researcher at The Scripps Research Institute.

"There's a difference between what is legal and what is ethical," said Loring, who attended the meeting. "And he's going to be pushing the needle a lot more toward the ethical side without worrying whether he can get away with stuff."

John Simpson of Santa Monica-based Consumer Watchdog, who has often criticized CIRM for conflicts of interest, also praised the decision.

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MS stem cell therapy treatment hope for mum

Posted: July 25, 2014 at 4:45 am

July 24, 2014, 10:29 p.m.

A 60 MINUTES report on new multiple sclerosis stem cell therapy has thrown Wendouree mum Kathryn Johnston a potential lifeline.

A 60 MINUTES report on new multiple sclerosis stem cell therapy has thrown Wendouree mum Kathryn Johnston a potential lifeline.

Hopeful: Wendouree mum Kathryn Johnston is hoping new stem cell therapy treatment will help her be a more active mother to her daughter Dellah, 7. PICTURE: KATE HEALY

Ms Johnston, who has had MS for 15 years, is hoping the treatment will help her be a more active mother to daughter Dellah, 7.

I cant do a great deal with my daughter now but its also the unknown not knowing if Ill wake up one day and not be able to walk, Ms Johnston said.

The 35-year-old emergency nurse hopes to travel to Russia in August next year for the treatment, which involves extracting her stem cells, freezing them while she undergoes a strong course of chemotherapy and then replacing them.

It gets rid of any underlying MS and rebuilds the immune system from scratch. As a general rule, its been about 80 per cent effective.

Ms Johnston first noticed her MS symptoms as an active Ararat 20-year-old doing her nursing degree and about to marry her childhood sweetheart Andrew.

I developed numbness in both hands but thought Id just slept on them until my tummy went numb too.

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The New York Stem Cell Foundation Partners With Beyond Batten Disease Foundation to Fight Juvenile Batten Disease

Posted: July 25, 2014 at 4:45 am

New York, NY (PRWEB) July 23, 2014

The New York Stem Cell Foundation (NYSCF) and Beyond Batten Disease Foundation (BBDF) have partnered to develop stem cell resources to investigate and explore new treatments and ultimately find a cure for juvenile Batten disease, a fatal illness affecting children.

NYSCF scientists will create induced pluripotent stem (iPS) cell lines from skin samples of young people affected by juvenile Batten disease as well as unaffected family members. IPS cell lines are produced by artificially turning back the clock on skin cells to a time when they were embryonic-like and capable of becoming any cell in the body. Reprogramming juvenile Batten iPS cells to become brain and heart cells, will provide the infrastructure needed to investigate what is going wrong with the cells adversely affected by the disease. Thus far, efforts to study juvenile Batten disease have been done using rodent models or human skin cells; neither of which accurately mimic the disease in the brain, leaving researchers without proper tools to study the disease or a solid platform for testing drugs that prevent, halt, or reverse its progression. This will be the largest and first genetically diverse collection of human iPS cells for a pediatric brain disease.*

In addition to working with BBDF to actively recruit patients and families to donate skin samples, Batten Disease Support and Research Association (BDSRA) is providing resources and technical support, spreading awareness among academic scientists, and notifying its Pharmaceutical partners. Together, BBDF and BDSRA will ensure that juvenile Batten disease and other researchers are aware of and utilize the 48 stem cell lines resulting from this collaboration to further juvenile Batten disease research worldwide.

We know the genetic mutations associated with juvenile Batten disease. This partnership will result in stem cell models of juvenile Batten, giving researchers an unprecedented look at how the disease develops, speeding research towards a cure, said Susan L. Solomon, NYSCF Chief Executive Officer.

Working with NYSCF to generate functional neuronal subtypes from patients and families is a stellar example of one of our key strategies in the fight against juvenile Batten disease: creating resource technology with the potential to transform juvenile Batten disease research and accelerate our timeline to a cure, said Danielle M. Kerkovich, PhD, BBDF Principal Scientist.

Juvenile Batten disease begins in early childhood between the ages of five and ten. Initial symptoms typically begin with progressive vision loss, followed by personality changes, behavioral problems, and slowed learning. These symptoms are followed by a progressive loss of motor functions, eventually resulting in wheelchair use and premature death. Seizures and psychiatric symptoms can develop at any point in the disease.

Juvenile Batten disease is one disorder in a group of rare, fatal, inherited disorders known as Batten disease. Over 40 different errors (mutations) in the CLN3 segment of DNA (gene) have been attributed to juvenile Batten disease. The pathological hallmark of juvenile Batten is a buildup of lipopigment in the body's tissues. It is not known why lipopigment accumulates or why brain and eventually, heart cells are selectively damaged. It is, however, clear that we need disease-specific tools that reflect human disease in order to figure this out and to build therapy.

NYSCF is a world leader in stem cell research and production with a mission to find cures for the devastating diseases of our time, including juvenile Batten disease. NYSCF has developed the NYSCF Global Stem Cell ArrayTM, an automated robotic technology that standardizes and scales stem cell production and differentiation, enabling the manufacture and analysis of large numbers of identical cells from skin samples of patients. The Array technology allows for the production of large-scale iPS cells that have the potential to become any cell type in the body.

This collaboration brings together the expertise of these two leading non-profit organizations, the support of BDSRA, and the participation of affected families, to create and make available to researchers, juvenile Batten disease iPS cell lines. Building on the NYSCF Research Institutes leading stem cell expertise and unique automated technology and analytics, while taking advantage of the tremendous resources and expertise of BBDF, BDSRA and affected families, this collaboration will move research

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NYSCF partners with Beyond Batten Disease Foundation to fight juvenile Batten disease

Posted: July 25, 2014 at 4:45 am

PUBLIC RELEASE DATE:

23-Jul-2014

Contact: David McKeon dmckeon@nyscf.org 212-365-7440 New York Stem Cell Foundation

NEW YORK, NY -- The New York Stem Cell Foundation (NYSCF) and Beyond Batten Disease Foundation (BBDF) have partnered to develop stem cell resources to investigate and explore new treatments and ultimately find a cure for juvenile Batten disease, a fatal illness affecting children.

NYSCF scientists will create induced pluripotent stem (iPS) cell lines from skin samples of young people affected by juvenile Batten disease as well as unaffected family members. IPS cell lines are produced by artificially "turning back the clock" on skin cells to a time when they were embryonic-like and capable of becoming any cell in the body. Reprogramming juvenile Batten iPS cells to become brain and heart cells will provide the infrastructure needed to investigate what is going wrong with the cells adversely affected by the disease. Thus far, efforts to study juvenile Batten disease have been done using rodent models or human skin cells, neither of which accurately mimic the disease in the brain, leaving researchers without proper tools to study the disease or a solid platform for testing drugs that prevent, halt, or reverse its progression. This will be the largest and first genetically diverse collection of human iPS cells for a pediatric brain disease.

In addition to working with BBDF to actively recruit patients and families to donate skin samples, Batten Disease Support and Research Association (BDSRA) is providing resources and technical support, spreading awareness among academic scientists, and notifying its Pharmaceutical partners. Together, BBDF and BDSRA will ensure that juvenile Batten disease and other researchers are aware of and utilize the 48 stem cell lines resulting from this collaboration to further juvenile Batten disease research worldwide.

"We know the genetic mutations associated with juvenile Batten disease. This partnership will result in stem cell models of juvenile Batten, giving researchers an unprecedented look at how the disease develops, speeding research towards a cure," said Susan L. Solomon, NYSCF Chief Executive Officer.

"Working with NYSCF to generate functional neuronal subtypes from patients and families is a stellar example of one of our key strategies in the fight against juvenile Batten disease: creating resource technology with the potential to transform juvenile Batten disease research and accelerate our timeline to a cure," said Danielle M. Kerkovich, PhD, BBDF Principal Scientist.

Juvenile Batten disease begins in early childhood between the ages of five and ten. Initial symptoms typically begin with progressive vision loss, followed by personality changes, behavioral problems, and slowed learning. These symptoms are followed by a progressive loss of motor functions, eventually resulting in wheelchair use and premature death. Seizures and psychiatric symptoms can develop at any point in the disease.

Juvenile Batten disease is one disorder in a group of rare, fatal, inherited disorders known as Batten disease. Over 40 different errors (mutations) in the CLN3 segment of DNA (gene) have been attributed to juvenile Batten disease. The pathological hallmark of juvenile Batten is a buildup of lipopigment in the body's tissues. It is not known why lipopigment accumulates or why brain and eventually, heart cells are selectively damaged. It is, however, clear that we need disease-specific tools that reflect human disease in order to figure this out and to build therapy.

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StemGenex Gives Hope to Parkinsons Patients through New Stem Cell Clinical Study

Posted: July 24, 2014 at 12:48 pm

La Jolla, CA (PRWEB) July 23, 2014

StemGenex, the leading resource for adult adipose stem cell therapy in the US aimed at improving the lives of patients dealing with degenerative diseases today announced their newest clinical study for Parkinsons disease. StemGenex believes that a commitment to the safety and efficacy of stem cell therapy are paramount when providing care to patients with degenerative diseases.

This clinical study makes stem cell therapy accessible to the millions of individuals currently living with Parkinsons disease. The protocol used in these stem cell treatments is unique to StemGenex, having the possibility of being more effective than other stem cell treatments currently available. StemGenex has developed a multiple administration protocol for patients suffering from Parkinsons disease which includes targeted methods of stem cell delivery. Among these methods is a novel approach for delivering stem cells past the blood brain barrier an issue most stem cell treatments have been challenged by.

Principal Investigator Dr. Jeremiah McDole, Ph.D. stated, As is the case with most neurodegenerative conditions, there are few available drugs to treat Parkinsons disease. The handful of drugs that are available can only ameliorate symptoms and unfortunately, prolonged usage can create terrible side-effects. Further, these drugs do not halt disease progression or aid in the repair of established damage. Our goal is to provide regenerative medicine applications that address these critical issues. The study we are conducting is designed to provide us with a large amount of rigorously collected data so that we can better understand the clinical benefit of Parkinsons patients treated with stem cells.

This study is registered through The National Institutes of Health which can be found at http://www.clinicaltrials.gov and is being conducted under IRB approval. According to StemGenex Director of Patient Advocacy, Joe Perricone, It is important patients have access to top-tier stem cell therapy. By providing access to registered clinical studies through The National Institutes of Health, we are providing patients with the ability to choose a stem cell treatment center with the highest standard of care.

Rita Alexander, founder and president of StemGenex stated, Parkinson's disease affects a very small part of the brain but anyone suffering with this disease understands the negative impact on his or her life is very big, actually, enormous. Over the last several years we have observed significant improvement in the symptoms of Parkinsons patients through stem cell treatment. We are determined to be part of the solution and are eager to document and publish our findings in the next few years.

Stem cell treatment studies are currently being offered by StemGenex to patients diagnosed with Parkinsons disease and other degenerative neurological diseases. StemGenex takes a unique approach of compassion and empowerment while providing access to the latest stem cell therapies for degenerative neurological diseases including Multiple Sclerosis, Alzheimers disease, stroke recovery and others.

To find out more about stem cell therapy, contact StemGenex either by phone at (800) 609-7795 or email Contact(at)stemgenex(dot)com.

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New method for reducing tumorigenicity in induced pluripotent stem-cell based therapies

Posted: July 24, 2014 at 3:44 am

PUBLIC RELEASE DATE:

23-Jul-2014

Contact: Kathryn Ruehle kruehle@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY -- The potential for clinical use of induced pluripotent stem cell (iPSC) technology for transplant-based therapeutic strategies has previously been hindered by the risk of dysregulated cell growth, specifically the development of tumors. The ability to use etoposide treatment to halt teratoma formation in iPSCs for the treatment of heart disease, specifically acute myocardial infarction, is demonstrated in an article in Stem Cells and Development, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available on the Stem Cells and Development website.

In the article 'Inhibition of DNA topoisomerase II selectively reduces the threat of tumorigenicity following induced pluripotent stem cell-based myocardial therapy' Saranya Wyles, Andre Terzic, Timothy Nelson, and coauthors, Mayo Clinic (Rochester, MN), discovered a strategy that alone or in conjunction with other methods could significantly reduce the risk of a tumorigenic event occurring. Their work demonstrates how pretreatment with genotoxic etoposide significantly lowered the threat of abnormal growths by removing the contaminated pluripotent cells and establishing an adjunctive therapy to further harness the clinical value of iPSC-derived cardiac regeneration.

"For anyone seeking to exploit iPSC technology in a clinical setting, the Mayo Clinic has described a strategy that significantly mitigates the risk of tumor development. Furthermore, the paper provides benchmark strategies for assessing the localization and persistence of cell-based treatments in a preclinical model," says Editor-in-Chief Graham C. Parker, PhD, The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI.

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About the Journal

Stem Cells and Development is an authoritative peer-reviewed journal published 24 times per year in print and online. The Journal is dedicated to communication and objective analysis of developments in the biology, characteristics, and therapeutic utility of stem cells, especially those of the hematopoietic system. Complete tables of content and a free sample issue may be viewed on the Stem Cells and Development website.

About the Publisher

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A US Leader in Stem Cell Therapy – StemGenex – Video

Posted: July 24, 2014 at 3:42 am


A US Leader in Stem Cell Therapy - StemGenex
http://www.stemgenex.com/ - StemGenex offer patients access to cutting-edge adipose stem cell therapies for degenerative diseases, cosmetic enhancements and ...

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