Researchers Convert Stem Cells Into Insulin-Producing Cells

Written by Kristin Della Volpe

Researchers have developed a multistep protocol that converts human embryonic stem cells into insulin-producing cells that can reverse diabetes in approximately 40 days in an animal model—much faster than the 4 months required for cells produced with previous methods. The goal is to be able transplant these insulin-producing cells for the treatment of type 1 diabetes, researchers reported in a study published in the November issue of Nature Biotechnology.   

“We are a step closer to having an unlimited supply of insulin-producing cells to treat patients with Type 1 diabetes,” said senior author Timothy Kieffer, PhD, Professor, Department of Cellular and Physiological Sciences and the Department of Surgery, University of British Columbia, British Columbia, Canada. “The cells we have generated may produce a more rapid and predictable reversal of diabetes relative to transplant of pancreatic progenitor cells,” he added.

“We have not yet made fully functional cells in a dish, but we are very close,” Dr. Kieffer said. “The cells we make in the lab produce insulin, but are still immature and need the transplant host to complete the transformation into fully functioning cells.”

Additional Study Takes the Cells a Step Farther
“One of the challenges in this field is to produce cells that respond accurately to glucose and secrete the right amount of insulin,” commented Douglas A. Melton, PhD, Xander University Professor at Harvard Medical School and investigator of the Howard Hughes Medical Institute, both in Cambridge, MA. “The Rezania et al paper is a step closer to this goal,” Dr. Melton said.

Dr. Melton and colleagues’ research on this topic, published in the October issue of Cell, takes the cells one step farther by “producing cells that respond to multiple glucose challenges in vitro, and producing functional beta cells shortly after transplantation into mice,” Dr. Melton said. “Taken together, these papers represent an advance on the general idea of producing functional beta cells for patients. The next challenge is finding a way to protect the cells from destruction following transplantation into diabetics,” Dr. Melton said.

7-Step Protocol by Rezania et al
The 7-stage in vitro differentiation protocol developed by Rezania et al transforms stem cells into insulin-secreting pancreatic cells via a cell-culture method that builds upon protocols previously used to specify pancreatic progenitors. Stage 7 cells expressed key markers of mature pancreatic beta cells (eg, the transcription factors MAFA, PDX1, and NKX6.1), and the cells possessed glucose-stimulated insulin secretion.

“The stem cells are cultivated in the lab where they can be expanded into very large numbers,” Dr. Kieffer explained. “The process involves the step-wise addition of key factors to the cells, following a recipe that we and others have developed. The factors we add direct the cells away from their embryonic stem cell characteristics towards insulin producing pancreatic beta-cells,” Dr. Kieffer said.

Following transplantation of 1.25 million of the stage 7 cells into mice that were rendered diabetic by injections of the beta-cell toxin streptozotocin, blood glucose levels were reduced to levels that were not significantly different from pre-streptozotocin levels by 16 days, and normal fasting blood glucose levels were reached by 40 days post-transplant. 

November 21, 2014



Rezania A, Bruin JE, Arora P, et al. Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol. 2014;32(11):1121-1133.