Growing insulin-producing pancreatic islet cells could increase transplants in diabetics.

US scientists have developed 2 different strategies for growing insulin-producing pancreatic islet cells, breakthroughs that could dramatically increase the availability of transplantation to cure diabetes.

Researchers from the University of California at San Diego Cancer Center have developed the first human islet cell line that responds to glucose stimulation by secreting insulin, both in the test tube and in laboratory animals. Until now, no one has succeeded in growing large numbers of these cells in culture. Many problems still must be overcome, including maintaining stable islet cell function and eliminating any risk of tumor formation, said Fred Levine, MD, PhD, who announced his team's achievement at last month's American Diabetes Association's Annual Scientific Sessions in San Antonio, TX. Nonetheless, "this proof of principle-that it will be possible to use human [islet] cell lines as an unlimited source of cells for transplantation into people with diabetes-could lead us over the formerly insurmountable hurdle of the organ donor shortage," Levine said.

Another potential source of human islet cells is discarded pancreatic tissue, according to a report in the July 5 issue of the Proceedings of the National Academy of Sciences. Testing the idea that adult pancreatic duct cells might be able to revert to multipotent cells, which then can differentiate into islet cells when appropriately stimulated, scientists at Harvard Medical School in Boston, MA digested human pancreatic tissue that normally is discarded after isolating islets. They then grew the duct tissue in the laboratory and overlaid the single epithelial cell layer with a commercially available extracellular matrix. Over several weeks in this culture media, the cells grew, increased their insulin secretion 10- to 15-fold, and formed islet-like structures, which the team called cultivated human islet buds (CHIBs). When exposed to glucose, the cells increased their insulin secretion another 2.3-fold.

"Our first observation of the CHIBs was a eureka moment-the formation of 3-dimensional structures with islet buds was far more striking than we expected," said Susan Bonner Weir, MD. "Our [laboratory] approach, once optimized, might generate meaningful amounts of new human islets from tissue that otherwise would have been discarded. We're like alchemists changing lead into gold."

More than 16 million Americans have diabetes, which ranks as the sixth leading cause of death in the United States. Currently, the only candidates for transplant are people with type 1 (insulin-dependent/juvenile) diabetes, in which the body destroys the insulin-producing beta cells in the pancreas. If vast supplies of islet cells were available, transplantation could be extended to those with type 2 (non-insulin-dependent) diabetes, which typically develops in adulthood and results from insulin resistance coupled with relative insulin deficiency.