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Generation of functional human pancreatic ß cells in vitro.

Pagliuca, Felicia W; Millman, Jeffrey R; Gürtler, Mads; Segel, Michael; Van Dervort, Alana; Ryu, Jennifer Hyoje; Peterson, Quinn P; Greiner, Dale; Melton, Douglas A.
Cell; 159(2): 428-39, 2014 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-25303535
The generation of insulin-producing pancreatic ß cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation therapy in diabetes. However, insulin-producing cells previously generated from human pluripotent stem cells (hPSC) lack many functional characteristics of bona fide ß cells. Here, we report a scalable differentiation protocol that can generate hundreds of millions of glucose-responsive ß cells from hPSC in vitro. These stem-cell-derived ß cells (SC-ß) express markers found in mature ß cells, flux Ca(2+) in response to glucose, package insulin into secretory granules, and secrete quantities of insulin comparable to adult ß cells in response to multiple sequential glucose challenges in vitro. Furthermore, these cells secrete human insulin into the serum of mice shortly after transplantation in a glucose-regulated manner, and transplantation of these cells ameliorates hyperglycemia in diabetic mice.