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Islet Cell & Regenerative Biology

 

Seeking new ways to treat diabetes by repairing or replacing cells

How do tissues develop and maintain themselves, and how can damaged tissues be repaired or regrown?

Scientists in Joslin’s Section of Islet Cell and Regenerative Biology want to know the answers to these questions for insulin-producing beta cells and other key cells involved in type 1 and type 2 diabetes, as well as in complications from diabetes. Their work covers an enormous range of diabetes-related challenges, going all the way from basic research in worms to clinical trials.

In type 1 diabetes, the body’s own immune system wipes out its beta cells, which are housed in pancreatic “islets” along with other hormone-producing cells.  An eventual cure for type 1 will require not just a way to stop this immune attack but a replacement source of healthy and plentiful beta cells.

Joslin scientists have made many major contributions to the effort to develop such a source, most recently demonstrating in animal models that beta cells can form from pancreatic duct cells in adults.  Researchers also are studying ways to create beta cells from “induced pluripotent stem cells”, which are created from adult cells but offer many of the characteristics of embryonic stem cells.

In other beta-cell work, researchers are fleshing out details on a key molecular mechanism that must function correctly for beta cells to begin producing insulin appropriately; examining the damaging effects of high blood glucose levels on beta cells, which has implications for type 2 diabetes as well as type 1 diabetes; and collaborating with researchers at the Massachusetts Institute of Technology to exploit nanotechnology fabrication to encapsulate islet cells in ways that let them survive transplantation in more robust form.

Another lab looks at fundamental biological regulatory mechanisms in the C. elegans worm that are involved in cell differentiation processes (shedding light on how stem cells can morph into  differentiated cells such as beta cells) or that aid in the regulation of cellular stress (offering new insights into mechanisms that influence aging, and pathways that can create complications from diabetes). Work by many groups in this versatile model organism has generated many fundamental discoveries that are applicable to humans, and has led to three Nobel prizes in the last decade.

Other investigators examine related questions in developmental and stem cell biology. Research on adult blood stem cells has made significant discoveries about tissue repair and replacement, including the finding that in old mice exposed to blood from young mice, old blood stem cells begin to act like young ones. This surprising discovery implicates hormonal mechanisms in the aging and developmental potential of stem cells and demonstrates that in this case, aging can indeed be reversed.

Additionally, scientists are making major strides in understanding the causes of embryonic genetic damage in diabetic pregnancy and in investigating autoimmune attacks on the heart.