Journal
CELL
Volume 159, Issue 2, Pages 428-439Publisher
CELL PRESS
DOI: 10.1016/j.cell.2014.09.040
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Funding
- Harvard Stem Cell Institute
- Juvenile Diabetes Research Foundation
- NIH
- Helmsley Charitable Trust
- JPB Foundation
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The generation of insulin-producing pancreatic beta 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 beta cells. Here, we report a scalable differentiation protocol that can generate hundreds of millions of glucose-responsive beta cells from hPSC in vitro. These stem-cell-derived beta cells (SC-beta) express markers found in mature beta cells, flux Ca2+ in response to glucose, package insulin into secretory granules, and secrete quantities of insulin comparable to adult beta 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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