Generation of functional human pancreatic β cells in vitro

  • Cell. 2014 Oct 9;159(2):428-39. doi: 10.1016/j.cell.2014.09.040.
Felicia W Pagliuca  1 ,  Jeffrey R Millman  1 ,  Mads Gürtler  1 ,  Michael Segel  1 ,  Alana Van Dervort  1 ,  Jennifer Hyoje Ryu  1 ,  Quinn P Peterson  1 ,  Dale Greiner  2 ,  Douglas A Melton  3
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: [email protected].
PMID: 25303535 DOI: 10.1016/j.cell.2014.09.040
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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