کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2035497 | 1072178 | 2014 | 12 صفحه PDF | دانلود رایگان |
• 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
SummaryThe 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.
Graphical AbstractFigure optionsDownload high-quality image (143 K)Download as PowerPoint slide
Journal: - Volume 159, Issue 2, 9 October 2014, Pages 428–439