Commercially available human embryonic stem cells (hESCs) have been induced to differentiate into fully functional pancreatic beta cells that were capable of restoring insulin production and regularizing glucose metabolism in two different rodent diabetes models.

Investigators at the University of British Columbia (Vancouver, Canada) and their colleagues at the biotechnology firm BetaLogics (Raritan, NJ, USA) developed a protocol to differentiate commercially available human embryonic stem cells (hESCs) in vitro into a highly enriched PDX1+ pancreatic progenitor cell population. These cells progressed in vivo into mature pancreatic endocrine cells.

Immature pancreatic precursor cells were transplanted into immunodeficient mice with streptozotocin-induced diabetes. Glycemia was initially controlled with exogenous insulin; however, as insulin levels derived from the grafted stem cells increased over time, the mice were weaned from the insulin. Glucose metabolism was eventually regulated by meal and glucose challenges. Similar differentiation of pancreatic precursor cells was observed after transplant into immunodeficient rats.

Additional details published in the June 27, 2012, online edition of the journal Diabetes revealed that throughout the in vivo maturation period hESC-derived endocrine cells exhibited gene and protein expression profiles that were remarkably similar to that of cells in the developing human fetal pancreas.

"We are very excited by these findings, but additional research is needed before this approach can be tested clinically in humans," said senior author Dr. Timothy Kieffer, professor of cellular and physiological sciences at the University of British Columbia. "The studies were performed in diabetic mice that lacked a properly functioning immune system that would otherwise have rejected the cells. We now need to identify a suitable way of protecting the cells from immune attack so that the transplant can ultimately be performed in the absence of any immunosuppression."

Related Links:
University of British Columbia
BetaLogics