[HTML][HTML] Generation of functional human pancreatic β cells in vitro

FW Pagliuca, JR Millman, M Gürtler, M Segel… - Cell, 2014 - cell.com
FW Pagliuca, JR Millman, M Gürtler, M Segel, A Van Dervort, JH Ryu, QP Peterson…
Cell, 2014cell.com
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 …
Summary
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.
cell.com