J.Jpn. Surg. Soc.. 113(5): 451-455, 2012

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Feature topic

REGENERATIVE MEDICINE BY REGENERATING ISLETS: PRESENT AND FUTURE THERAPIES FOR DIABETES

β cell replacement by islet transplantation is a promising clinical therapy for patients with type 1 diabetes because it satisfies safety issues and offers reliability in controlling blood glucose levels. One remaining problem is that it requires islets from two to three donor pancreases to achieve insulin independence, thus aggravating the donor shortage. Islet regeneration in vivo and generation of β cells ex vivo followed by transplantation represent attractive therapeutic methods to restore the β cell mass. Recent studies have suggested a number of postnatal pancreatic epithelial cells as candidate sources for future β cell replacement therapy. β cells can reenter the cell cycle after a brief quiescent stage, suggesting the potential for engineering for expansion. The mechanisms of α cell-to-β cell transdifferentiation can also be utilized to increase the β cell population. Pancreatic ductal cells can proliferate and differentiate into regenerated β cells. Pancreatic acinar cells are also observed to transdifferentiate into endocrinal cells, although infrequently under in vivo conditions. After a few more series of careful studies performed on human cells, the ultimate goal of translation to the clinic appears to be just around the corner. Islet cell transplantation will become a welcome new form of cell-regeneration therapy.

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