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      Generation of functional human pancreatic β cells in vitro.

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          Abstract

          The generation of insulin-producing pancreatic β 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 β cells. Here, we report a scalable differentiation protocol that can generate hundreds of millions of glucose-responsive β cells from hPSC in vitro. These stem-cell-derived β cells (SC-β) express markers found in mature β cells, flux Ca(2+) in response to glucose, package insulin into secretory granules, and secrete quantities of insulin comparable to adult β 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.

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          Author and article information

          Journal
          Cell
          Cell
          Elsevier BV
          1097-4172
          0092-8674
          Oct 09 2014
          : 159
          : 2
          Affiliations
          [1 ] Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
          [2 ] Diabetes Center of Excellence, University of Massachusetts Medical School, 368 Plantation Street, AS7-2051, Worcester, MA 01605, USA.
          [3 ] Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA. Electronic address: dmelton@harvard.edu.
          Article
          S0092-8674(14)01228-8 NIHMS631806
          10.1016/j.cell.2014.09.040
          4617632
          25303535

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