Abstract
Objective Bone marrow mesenchymal stem cell (BM-MSC) transplantation has generated a great deal of excitement as a promising therapeutic strategy for diabetes mellitus. However, the exact mechanisms of reversing hyperglycemia remain elusive. Our objective was to investigate whether stem cell differentiation determined therapeutic efficacy. Materials and Methods Wistar rats were rendered diabetic by an intraperitoneal injection of streptozotocin. BM-MSCs isolated from diabetic Wistar rats were analyzed for phenotype characteristics. Subsequently, BM-MSCs were transplanted into diabetic rats, followed by intravenous injection of recombinant lentiviruses encoding 2 different small hairpin RNAs (shRNAs) for specific interference with neurogenin 3 (Ngn3). We measured blood glucose levels and insulin and performed histological analysis of the pancreas. Results BM-MSCs lowered blood glucose by increasing β-cell mass compared with sham-operated controls, but this effect was inhibited by interference with the Ngn3 gene. Conclusion Differentiation of stem cells, including BM-MSCs and endogenous pancreatic stem cells, plays a major role in the process of reversing hyperglycemia.
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