With human embryonic stem cells as a starting point, the scientists were for the first time able to produce, in the kind of massive quantities needed for cell transplantation and pharmaceutical purposes, human insulin-producing beta cells equivalent in most every way to normally functioning beta cells.
The researchers wrote in their 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."
Doug Melton, who led the work and who 23 years ago, when his then infant son Sam was diagnosed with type 1 diabetes, dedicated his career to finding a cure for the disease, said he hopes to have human transplantation trials using the cells to be underway within a few years. "We are now just one pre-clinical step away from the finish line," said Melton, whose daughter Emma also has type 1 diabetes. "You never know for sure that something like this is going to work until you’ve tested it numerous ways," said Melton, Harvard’s Xander University Professor and a Howard Hughes Medical Institute Investigator. "We’ve given these cells three separate challenges with glucose in mice and they’ve responded appropriately; that was really exciting.
"It was gratifying to know that we could do something that we always thought was possible," he continued, "but many people felt it wouldn’t work. If we had shown this was not possible, then I would have had to give up on this whole approach. Now I’m really energized."
The stem cell-derived beta cells are presently undergoing trials in animal models, including non-human primates, Melton said.
Harvard Stem Cell Institute