Human embryonic stem cell therapy was recently shown to reverse type 1 diabetes in mice, and now new mouse studies suggest a role for stem cells in the treatment of type 2 diabetes…
Obese, diabetic mice treated with a combination of transplanted stem cell-derived pancreatic progenitor cells and insulin-sensitizing drugs showed improved glucose metabolism and rapid weight loss. Mice receiving an antidiabetes drug without the stem cell transplants remained glucose intolerant.
Researcher Timothy J. Kieffer, PhD, of the University of British Columbia, Vancouver, Canada, and colleagues wrote that, “Stem cell-based treatments may prove to be an effective therapeutic strategy for type 2 diabetes.
Dr. Kieffer added that, “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.” “Thus, stem cells are candidates for restoring functional beta cells in an insulin-resistant, obese setting.”
In earlier research, Kieffer and colleagues first showed that hESC-derived pancreatic progenitor cells reversed diabetes in a mouse model of type 1 diabetes. The research team has also recently developed a seven-stage protocol to more quickly convert hESC into insulin-secreting pancreatic cells, which was shown to rapidly reverse diabetes in the type 1 diabetes mouse model within 40 days.
Based on evidence showing that, like patients with type 1 diabetes, those with type 2 diabetes have reduced beta cell mass and declining beta cell function during the transition to active disease, the researchers hypothesized that hESC-derived insulin-secreting cells may also be effective in this patient population.
Kieffer and colleagues first had to develop a type 2 diabetes mouse model, since the study design made transplanting human progenitor cells into traditional models not feasible.
They did this by feeding SCID-beige mice a 45%-60% fat diet for seven weeks, which induced many characteristics of type 2 diabetes, including increased body weight, fasting hyperglycemia, glucose intolerance, insulin resistance, and hyperleptinemia.
“Exposure to high-fat diets did not impact the maturation of macro-encapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in high-fat diet-fed transplant recipients after 24 weeks,” the researchers wrote.
But stem cell transplantation alone did not fully reverse the diet-induced hyperglycemia and obesity.
In an effort to improve responses, a second cohort of high-fat diet fed mice were treated with the pancreatic progenitor cell transplants combined with one of three diabetes drugs – metformin, rosiglitazone, or sitagliptin.
All three combination treatments were found to rapidly reduce body weight, and the combinations that included metformin or sitagliptin also improved hyperglycemia within four months.
Sitagliptin, which acts to increase circulating incretin levels by preventing DPP4 inactivation, was the most effective drug tested. When the stem cell therapy was combined with sitagliptin, glucose tolerance and body weight was similar in the high-fat diet mice at 12 weeks post-transplantation to that of low-fat diet fed control mice.
Transplanted mice treated with either metformin or sitagliptin had reduced fasting C-peptide levels, suggesting that the pancreas was no longer compensating for insulin resistance.
“The reversal of hyperleptinemia in both sitagliptin- and metformin-treated transplant recipients also suggests a more robust reversal of the obesity phenotype in these groups as compared with the high-fat diet transplant recipients treated with rosiglitazone or without drugs,” the researchers wrote.
“Taken together, our data suggest that a cell-based insulin replacement therapy could be considered as a future treatment option for type 2 diabetes, particularly if combined with antidiabetic drugs.”
- Note that this mouse study demonstrated that the administration of human embryonic stem-cell derived pancreatic progenitor cells + an anti-diabetes drug can ameliorate a type-2 diabetes-like phenotype.
- Be aware that adequate controls (including mice given an anti-diabetes drug but not stem cells) showed no amelioration of the phenotype.
- Sitagliptin, which acts to increase circulating incretin levels by preventing DPP4 inactivation, was the most effective drug tested.
Bruin JE, et al “Treating diet-induced diabetes and obesity with human embryonic stem cell-derived pancreatic progenitor cells and antidiabetic drugs” Stem Cell Reports 2015; 4: 1-16.