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Building beta cells from human stem cells

Many years of research into the biology of insulin-producing β (beta) cells has culminated in the discovery of a method to produce β cells from human stem cells. Islet transplantation—during which pancreatic islets, including β cells, are transplanted into people whose own β cells are not functioning properly—is a promising experimental treatment for type 1 diabetes. However, islet transplantation has been hindered, in part, by the limited quantities of donor islets. The field of stem cell biology has offered hope that islets could be produced in the laboratory. Stem cells are pluripotent, meaning they are able to produce any type of cell in the body, and induced pluripotent stem cells can be made by “reprogramming” adult cells. Previous attempts to produce islets in the lab by differentiating, or maturing, human stem cells into β cells have generated cells that produce insulin, but which lack several important β cell-like qualities, such as a finely tuned response to changing glucose levels.

Drawing on this previous research, scientists sought to improve on these results by testing over 70 chemical compounds in over 150 combinations. They developed an optimized, multistep process utilizing 11 of these compounds in a precise sequence over the course of 4-5 weeks. By the end of this process, the researchers had coaxed large numbers of both human embryonic stem cells1 and induced pluripotent stem cells (which can be made from adult cells, including cells from those with type 1 diabetes) into a state that closely resembles naturally-occurring β cells. Importantly, these “stem-cell-derived β cells” (SC-βcells) are similar to pancreatic β cells and respond to fluctuating glucose levels by increasing or decreasing secretion of insulin, as appropriate. To test whether they might be therapeutically useful, the researchers transplanted human embryonic stem cell-derived SC-β cells into mice genetically engineered to display type 1 diabetes-like symptoms. After 2 weeks, the SC-β cells were producing significant amounts of insulin in response to glucose and prevented the mice from developing dangerously high blood glucose levels.

Although the process will need to be adapted for large-scale manufacturing, and further tests must be conducted to determine if SC-β cells can be a long-term replacement for β cells in people, this dramatically improved process for making large amounts of β cells is a promising step toward developing therapeutic stem cell therapies. SC-β cell technology may lead to advances in treating diabetes and in artificial organ development, especially if ways to protect newly transplanted β cells from the autoimmune attack are developed. Additionally, SC-β cells offer a valuable new resource for investigating beta cell biology and disease modeling, as well as opportunities for drug screening and testing novel potential therapies.


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