P Lin1, L Chen, N Yang, Y Sun, Y X Xu. 1. Department of Endocrinology, Qilu Hospital, Shandong University, Shandong, China.
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 beta-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.
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 diabeticWistar rats were analyzed for phenotype characteristics. Subsequently, BM-MSCs were transplanted into diabeticrats, 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 beta-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.