In a new study published in the journal Stem Cell Reports, researchers reveal that a combination of stem cell transplantation and anti-diabetic medication was able to successfully treat mice with type 2 diabetes. The findings could set the stage for clinical trials to test the first stem cell-based approach for insulin replacement in patients with type 2 diabetes.
It is estimated that about 400 million people worldwide have diabetes and type 2 diabetes accounts for 90-95% of them. The condition occurs due to inability of the body to produce enough insulin or use it effectively. This results in high blood glucose levels which lead to further secondary complications. It is currently treated with oral medication and/or in combination with insulin injections. This therapy regimen however leads to GI problems, weight gain, extremely low blood glucose or non-responsiveness of patients. To address these complications, senior author Timothy Kieffer of the University of British Columbia collaborated with BetaLogics, a division of Janssen Research & Development, LLC and decided to try a stem cell based approach.
Kieffer’s group fed mice a high-fat diet to induce obesity, low responsiveness to insulin, and high blood glucose levels–the hallmarks of type 2 diabetes. These mice were then transplanted with encapsulated pancreatic progenitor cells derived from human embryonic stem cells. Upon maturation into insulin-secreting beta cells, improvements were seen with respect to insulin sensitivity and glucose metabolism. Moreover, stem cell transplantation combined with currently available antidiabetic drugs resulted in rapid weight loss in the mice and more significant improvements in glucose metabolism compared with either treatment alone. When the stem-cell therapy was combined with Sitagliptin, glucose tolerance and body weight were similar in the high-fat diet mice at 12 weeks post-transplantation to that of low-fat diet fed control mice.
“Our data suggest that transplanted human embryonic stem-cell (hESC)-derived insulin-producing cells thrive following chronic exposure to high-fat diets, at least in immunodeficient mice,” the researchers wrote. “Thus, stem cells are candidates for restoring functional beta cells in an insulin-resistant, obese setting.”
Kieffer’s group wants to take this research further and test whether transplanting more cells would lead to faster reversal of symptoms and also at a lower dose as compared to pancreatic progenitor cells. There are other aspects of the study also that need further explanations. “Their weight loss was intriguing, because some of the common diabetes therapies often lead to weight gain,” Kieffer said. “We need to do more studies to understand how the cell transplants lead to weight loss.”
He is however optimistic to develop this line of research into an effective therapy. “Success in these clinical trials could pave the way for testing in patients with type 2 diabetes,” Kieffer says. “Our hope is that a stem cell-based approach to insulin replacement will ultimately improve glucose control in patients with both type 1 and type 2 diabetes, resulting in healthier, longer lives.”
The original publication can be accessed here.