VANCOUVER In a world's first, University of B.C. scientists have used human embryonic stem cell transplants to reverse diabetes in mice.

A 13-member team, whose work was published Wednesday in the journal Diabetes, showed that as the stem cells matured into insulin-secreting cells (beta-cells in the pancreas), a few dozen diabetic mice were weaned gradually off insulin over a period of months.

The study, which cost at least $500,000, was funded by the Canadian Institutes of Health Research, the Stem Cell Network of Canada, Stem Cell Technologies of Vancouver, the Juvenile Diabetes Research Foundation and the Michael Smith Foundation of Health Research. About half the research team was comprised of scientists from the New Jersey private research and development arm (BetaLogics Venture) of Janssen Pharmaceuticals.

"It took about four to five months for the (stem) cells to become functional in our experiments and the mice were able to maintain good blood glucose levels even when fed a high-glucose diet," said lead author Timothy Kieffer, a UBC professor in the department of cellular and physiological sciences.

Type 1 otherwise known as juvenile diabetes is an autoimmune disease in which a patient's immune system kills off insulin-producing cells in the pancreas. Typically, patients must inject themselves with insulin or use insulin pumps to control their blood glucose levels.

While pancreatic islet cell transplantation pioneered at the University of Alberta several years ago has been shown to be an effective way of reducing dependence on insulin injections, such treatments are costly and cumbersome since they require cells culled from dead bodies; such cells are always in short supply. As well, islet cell transplant patients must forever take anti-rejection drugs that can cause organ damage.

Although the research showed that stem cells have great potential as a diabetes cure, it also revealed there are still a few pitfalls to overcome before agencies like the Food and Drug Administration in the United States or Health Canada approve such a therapy. Some mice developed bone or cartilage growths in areas where the cells were inserted, an unacceptable side-effect that future experiments must resolve.

Another obstacle is that the mice used in the study weren't typical; they were a special strain, bred to be immuno-compromised so they wouldn't reject the human cells as foreign invaders. Studies are continuing at UBC, in many more mice, to determine the feasibility of encapsulating stem cells in a membrane material that won't be recognized as a foreign body and rejected.

Kieffer said he's extremely encouraged by the fact that the mice not only were weaned off their need for insulin but also lived well and long, even though they were bred to be immune-deficient. Still, he said, researchers must find ways to fine-tune the approach so that cells don't evolve into something other than what's desired.

In the early stages of the experiment, some mice developed fluid-filled cysts, a problem that was rectified in the laboratory with a cell culture medium change.

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Canadian scientists use stem cells to reverse diabetes in mice

Public release date: 27-Jun-2012 [ | E-mail | Share ]

Contact: Rolf Kemler kemler@ie-freiburg.mpg.de 49-761-510-8471 Max-Planck-Gesellschaft

This release is available in German.

Scientists at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg have gained important insights for stem cell research which are also applicable to human tumours and could lead to the development of new treatments. As Rolf Kemler's research group discovered, a molecular link exists between the telomerase that determines the length of the telomeres and a signalling pathway known as the Wnt/-signalling pathway.

Telomeres are the end caps of chromosomes that play a very important role in the stability of the genome. Telomeres in stem cells are long and become shorter during differentiation or with age, but lengthen again in tumour cells.

The Wnt/-catenin signalling pathway controls numerous processes in embryonic development, such as the formation of the body axis and of organ primordia, and is particularly active in embryonic and adult stem cells. The -catenin protein plays a key role in this signalling pathway. The incorrect regulation or mutation of -catenin leads to the development of tumours.

Rolf Kemler's research group has now shown that -catenin regulates the telomerase gene directly, and has explained the molecular mechanism at work here. Embryonic stem cells with mutated -catenin generate more telomerase and have extended telomeres, while cells without -catenin have low levels of telomerase and have shortened telomeres.

This regulation mechanism can also be found in human cancer cells. These discoveries could lead to the development of a new approach to the treatment of human tumours.

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Original publication: Wnt/-Catenin Signaling Regulates Telomerase in Stem Cells and Cancer Cells Katrin Hoffmeyer, Angelo Raggioli, Stefan Rudloff, Roman Anton, Andreas Hierholzer, Ignacio Del Valle, Kerstin Hein, Riana Vogt, Rolf Kemler Science 22 June 2012: Vol. 336 no. 6088 pp. 1549-1554 DOI: 10.1126/science.1218370

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Regulation of telomerase in stem cells and cancer cells

Public release date: 27-Jun-2012 [ | E-mail | Share ]

Contact: Clare Ryan clare.ryan@ucl.ac.uk 44-203-108-3846 University College London

Stem cells from patients with a rare form of muscular dystrophy have been successfully transplanted into mice affected by the same form of dystrophy, according to a new study published today in Science Translational Medicine.

For the first time, scientists have turned muscular dystrophy patients' fibroblast cells (common cells found in connective tissue) into stem cells and then differentiated them into muscle precursor cells. The muscle cells were then genetically modified and transplanted into mice.

The new technique, which was initially developed at the San Raffaele Scientific Institute of Milan and completed at UCL, could be used in the future for treating patients with limb-girdle muscular dystrophy (a rare form in which the shoulders and hips are primarily affected) and, possibly, other forms of muscular dystrophies.

Muscular dystrophies are genetic disorders primarily affecting skeletal muscle that result in greatly impaired mobility and, in severe cases, respiratory and cardiac dysfunction. There is no effective treatment, although several new approaches are entering clinical testing including cell therapy.

In this study, scientists focused on genetically modifying a type of cell called a mesoangioblast, which is derived from blood vessels and has been shown in previous studies to have potential in treating muscular dystrophy. However, the authors found that they could not get a sufficient number of mesoangioblasts from patients with limb-girdle muscular dystrophy because the muscles of the patients were depleted of these cells.

Instead, scientists in this study "reprogrammed" adult cells from patients with limb-girdle muscular dystrophy into stem cells and were able to induce them to differentiate into mesoangioblast-like cells. After these 'progenitor' cells were genetically corrected using a viral vector, they were injected into mice with muscular dystrophy, where they homed-in on damaged muscle fibres.

The researchers also showed that when the same muscle progenitor cells were derived from mice the transplanted cells strengthened damaged muscle and enabled the dystrophic mice to run for longer on a treadmill than dystrophic mice that did not receive the cells.

Dr Francesco Saverio Tedesco, UCL Cell & Developmental Biology, who led the study, said: "This is a major proof of concept study. We have shown that we can bypass the limited amount of patients' muscle stem cells using induced pluripotent stem cells and then produce unlimited numbers of genetically corrected progenitor cells.

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Successful transplant of patient-derived stem cells into mice with muscular dystrophy

Public release date: 27-Jun-2012 [ | E-mail | Share ]

Contact: Bridget Dempsey b.dempsey@qmul.ac.uk 44-207-882-7927 Queen Mary, University of London

Scientists at Queen Mary, University of London have uncovered a link between two genes which shows how stem cells could develop into cancer.

The research, published in the online journal PLoS ONE, found a novel mechanism which could be the catalyst for stem cells changing into a tumour.

Dr Ahmad Waseem, a reader in oral dentistry at Queen Mary, University of London who led the research, said: "It was quite an unexpected discovery. We set out to investigate the role of the stem cell gene Keratin K15 which was thought to be a biomarker for normal stem cells.

"Through our research, we discovered there was link between K15 and the notorious cancer gene FOXM1. We found FOXM1 could target K15 to induce cancer formation."

Cancer develops when there is a problem with stem cells; the cells that carry out internal repairs throughout the human body. The loss of stem cell function leads to uncontrolled growth which ultimately develops into a tumour.

The team went through a process where they used extremely sensitive cell and molecular approaches to establish this link.

The study, funded by the Facial Surgery Research Foundation, Saving Faces, paves the way towards identifying new anti-cancer drugs which could be tailored towards cancer stem cells.

Consultant oral and maxillofacial surgeon Professor Iain Hutchison, founder of Saving Faces and co-author on the study, said: "We are excited about this finding as it could lead to more effective cancer drugs being developed to target cancer stem cells and prevent cancer recurrence."

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Scientists identify new cancer stem cell mechanism

Public release date: 27-Jun-2012 [ | E-mail | Share ]

Contact: Brian Kladko brian.kladko@ubc.ca 604-827-3301 University of British Columbia

University of British Columbia scientists, in collaboration with an industry partner, have successfully reversed diabetes in mice using stem cells, paving the way for a breakthrough treatment for a disease that affects nearly one in four Canadians.

The research by Timothy Kieffer, a professor in the Department of Cellular and Physiological Sciences, and scientists from the New Jersey-based BetaLogics, a division of Janssen Research & Development, LLC, is the first to show that human stem cell transplants can successfully restore insulin production and reverse diabetes in mice. Crucially, they re-created the "feedback loop" that enables insulin levels to automatically rise or fall based on blood glucose levels. The study is published online today in the journal Diabetes.

After the stem cell transplant, the diabetic mice were weaned off insulin, a procedure designed to mimic human clinical conditions. Three to four months later, the mice were able to maintain healthy blood sugar levels even when being fed large quantities of sugar. Transplanted cells removed from the mice after several months had all the markings of normal insulin-producing pancreatic cells.

"We are very excited by these findings, but additional research is needed before this approach can be tested clinically in humans," says Kieffer, a member of UBC's Life Sciences Institute. "The studies were performed in diabetic mice that lacked a properly functioning immune system that would otherwise have rejected the cells. We now need to identify a suitable way of protecting the cells from immune attack so that the transplant can ultimately be performed in the absence of any immunosuppression."

The research was supported by the Canadian Institutes of Health Research, the Stem Cell Network of Canada, Stem Cell Technologies of Vancouver, the JDRF and the Michael Smith Foundation for Health Research.

Diabetes results from insufficient production of insulin by the pancreas. Insulin enables glucose to be stored by the body's muscle, fat and liver and used as fuel; a shortage of insulin leads to high blood sugar that raises the risk of blindness, heart attack, stroke, nerve damage and kidney failure.

Regular injections of insulin are the most common treatment for the type 1 form of this disease, which often strikes young children. Although experimental transplants of healthy pancreatic cells from human donors have shown to be effective, that treatment is severely limited by the availability of donors.

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Stem cells can beat back diabetes: UBC research

Anda Berada di Sini : Dunia Berita

28 Jun, 2012 10:53 AM

Human Stem Cells Reverse Diabetes In Mice: Research

VANCOUVER, June 28 (Bernama) -- A new research has shown that human stem cell transplants can successfully restore insulin production and reverse diabetes in mice for the first time, China's Xinhua news agency reported.

The study, conducted by scientists from University of British Columbia (UBC) and the New Jersey-based BetaLogics, a division of Janssen Research & Development, LLC, could pave the way for a breakthrough treatment for the disease.

After the stem cell transplant, the diabetic mice were weaned off insulin, a procedure designed to mimic human clinical conditions, according to the study published online Wednesday in the journal Diabetes.

Three to four months later, the mice were able to maintain healthy blood sugar levels even when being fed large quantities of sugar.

"We are very excited by these findings, but additional research is needed before this approach can be tested clinically in humans," said Timothy Kieffer, one of the 13 authors and a professor from UBC.

Kieffer said that the studies were performed in diabetic mice that lacked a properly functioning immune system that would otherwise have rejected the cells.

He added that they now need to identify a suitable way of protecting the cells from immune attack so that the transplant can ultimately be performed in the absence of any immunosuppression.

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Human Stem Cells Reverse Diabetes In Mice: Research