Destruction of insulin-producing beta cells in the pancreas is at the heart of type 1 and type 2 diabetes. "We are looking for ways to make new beta cells for these patients to one day replace daily insulin injections," says Ben Stanger, M.D., Ph.D., assistant professor of Medicine in the Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania. Transplanting islet cells to restore normal blood sugar levels in patients with severe type 1 diabetes is one approach to treating the disease, and using stem cells to create beta cells is another area of investigation. However, both of these strategies have limitations: transplantable islet cells are in short supply, and stem cell-based approaches have a long way to go before they reach the clinic. "It's a powerful idea that if you have the right combination of transcription factors you can make any cell into any other cell. It's cellular alchemy," comments Dr. Stanger. New research from Dr. Stanger and postdoctoral fellow Yi-Ju Chen, Ph.D., together with a host of colleagues, reported online on March 6, 2014 in an open-access article in Cell Reports, describes how introducing three proteins that control the regulation of DNA in the nucleus -- called transcription factors -- into an immune-deficient mouse turned a specific group of cells in the gut lining into beta-like cells, raising the prospect of using differentiated pancreatic cells as a source for new beta cells. In 2008, the lab of Dr. Stanger's postdoctoral mentor introduced the three beta-cell reprogramming factors -- Pdx1 (P), MafA (M), and Ngn3 (N) -- collectively called PMN – into the acinar cells of the pancreas. Remarkably, this manipulation caused the cells to take on some structural and physiological features of beta cells.
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