Robarts Research Institute accelerates stem cell biology

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The 7,000 sq. ft. Krembil Centre for Stem Cell Biology opened in the fall of 2003 at Robarts Research Institute, thanks in large part to a $5 million gift from the Krembil Foundation in Toronto. That increased investment – further enhanced by $4.8 million from the Ontario Research and Development Challenge Fund and $2 million from the Canada Foundation of Innovation – is accelerating the stem cell research programs underway at Robarts.

“If the Human Genome Project is like knowing the keys on a piano, stem cells will tell you which notes to play,” says Dr. Mick Bhatia, Krembil Chair in Stem Cell Biology and Director of the stem cell biology program at Robarts, which has increased from one scientist with a half-time technician in 1998 to three scientists with more than 30 scientific personnel.

Dr. Arthur Brown, a developmental biologist, recently joined the group from Robarts and in 2003 the Institute recruited Dr. Melissa Carpenter, former Director of Stem Cell Biology, from Geron Corporation, a San Francisco Bay-area biotech company that collaborates widely with research institutes and universities worldwide.

Among the papers the Robarts stem cell biology group has published in the last year is a study led by Dr. Bhatia, highlighted on the cover of the July 2003 issue of Nature Biotechnology, which provided the first evidence that adult stem cells can induce pancreatic tissue to repair itself and reverse the symptoms associated with diabetes.

The study involves a series of experiments in which adult mice with diabetes symptoms from pancreatic damage were given transplants of bone marrow-derived stem cells. Blood sugar levels in the mice rapidly decreased seven days after transplant and, surprisingly, the once-damaged pancreases had regenerated large amounts of pancreatic tissue and were now able to produce insulin. As expected, all of the animals that did not receive transplants continued to exhibit high blood sugar, compared with 100 per cent of the transplanted mice, which had near normal blood sugar levels.

Most interesting to scientists is what has been revealed about the cellular mechanism that reversed the symptoms associated with diabetes. While recent excitement in the area of tissue repair has focused on the “transdifferentiation” potential of bone marrow-derived stem cells – their ability to become other cell types such as muscle, liver and brain cells – this study showed that transdifferentiation was not the mechanism that led to renewed insulin production. Instead, the bone marrow cells had induced the recipient’s own cells to proliferate throughout the pancreas, begin to produce insulin and subsequently control blood sugar.

While further investigation is required to understand more about the mechanism of renewed insulin production, this finding of bone marrow cells inducing tissue repair constitutes a significant paradigm shift in the study of adult stem cell biology and organ regeneration. “This paper represents a major advance in developing novel therapy for diabetes by using adult bone marrow stem cells to allow regeneration of patients’ own insulin producing islet cells and reversing the disease,” said Dr. Bhagirath Singh, Scientific Director of CIHR’s Institute of Infection and Immunity, and himself a leader in the field of diabetes and autoimmune disease.