TY - JOUR
T1 - Generation of functional human pancreatic β cells in vitro
AU - Pagliuca, Felicia W.
AU - Millman, Jeffrey R.
AU - Gürtler, Mads
AU - Segel, Michael
AU - Van Dervort, Alana
AU - Ryu, Jennifer Hyoje
AU - Peterson, Quinn P.
AU - Greiner, Dale
AU - Melton, Douglas A.
N1 - Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/10/9
Y1 - 2014/10/9
N2 - 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 Ca2+ 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.
AB - 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 Ca2+ 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.
UR - http://www.scopus.com/inward/record.url?scp=84910673362&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2014.09.040
DO - 10.1016/j.cell.2014.09.040
M3 - Article
C2 - 25303535
AN - SCOPUS:84910673362
SN - 0092-8674
VL - 159
SP - 428
EP - 439
JO - Cell
JF - Cell
IS - 2
ER -