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      Generation of functional human pancreatic β cells in vitro.

      Cell

      Animals, Cell Culture Techniques, Humans, Induced Pluripotent Stem Cells, cytology, metabolism, Insulin, genetics, Insulin-Secreting Cells, Islets of Langerhans, Mice, Pluripotent Stem Cells

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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. Copyright © 2014 Elsevier Inc. All rights reserved.

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          Journal
          25303535
          10.1016/j.cell.2014.09.040

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