Details

Autor(en) / Beteiligte

• Pagliuca, Felicia W.
• Millman, Jeffrey R.
• Gürtler, Mads
• Segel, Michael
• Van Dervort, Alana
• Ryu, Jennifer Hyoje
• Peterson, Quinn P.
• Greiner, Dale
• Melton, Douglas A.

Titel

Generation of Functional Human Pancreatic β Cells In Vitro

Ist Teil von

• Cell, 2014-10, Vol.159 (2), p.428-439

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •Stem-cell-derived β (SC-β) cells secrete insulin upon glucose stimulation in vitro•SC-β cells resemble human islet β cells by gene expression and ultrastructure•SC-β cell transplantation ameliorates hyperglycemia in mice•SC-β cells provide a platform for therapeutic development and disease modeling Functional pancreatic β cells are generated from human pluripotent stem cells using a scalable, in vitro differentiation protocol. This Resource provides a valuable platform for therapeutic development and disease modeling in diabetes.