A new study entitled “Generation of Functional Human Pancreatic β Cells In Vitro” published in online October issue of Cell reports a new method capable of generating functional insulin-producing pancreatic beta cells from human pluripotent stem cells.
In type 1 diabetes, the body destroys all patients’ beta cells, while in type 2, diabetes patients exhibit insulin resistance and beta cell dysfunction. These cells are the ones that allow people’s bodies to respond to blood sugar levels and control it by releasing insulin. Treating diabetes, particularly type 1, by transplanting new beta cells has been a long-term goal in the diabetes field; however, the scarce source of cells as well as their poor quality has been a major limitation.
Now, a team of scientists from Harvard University with Felicia W. Pagliuca, Jeff Millman, and Mads Gurtler as first authors, and led by Douglas Melton, report a new method that generates beta cells that respond to glucose and secrete insulin upon glucose stimulation in vitro. The stem-cell-derived beta (SC-beta) cells are similar to primary human beta cells, in both gene and protein expression. Moreover, SC-beta cells’ insulin granules are structurally similar to those in primary human beta cells. Notably, when transplanted into mice, SC-beta cells secrete insulin to the bloodstream within two weeks, with controls failing to produce detectable insulin levels in the same period. Finally, the authors showed translated SC- beta cells reversed hyperglycemia observed in diabetic hyperglycemia mice.
Thus, the authors suggest that generating SC- beta cells on this scale not only allow for pharmacogenetics studies, drug discovery, and understanding of human metabolism, but it also provides a stepping stone to a future generation of islets and pancreatic organs.
Elaine Fuchs, at Rockefeller University, and a Howard Hughes Medical Institute investigator, commented, “One of the most important advances to date in the stem cell field, and I join the many people throughout the world in applauding my colleague for this remarkable achievement. For decades, researchers have tried to generate human pancreatic beta cells that could be cultured and passaged long-term under conditions where they produce insulin. Melton and his colleagues have now overcome this hurdle and opened the door for drug discovery and transplantation therapy in diabetes.”
Jose Oberholzer, associate professor of surgery, endocrinology, diabetes, and bioengineering at the University of Illinois at Chicago, and director of the islet and pancreas transplant program and the chief of the Division of Transplantation, also noted the work “will leave a dent in the history of diabetes. Doug Melton has put in a lifetime of hard work in finding a way of generating human islet cells in vitro. He made it. This is a phenomenal accomplishment.”
