Protection of mouse pancreatic islet function by co-culture with hypoxia pre-treated mesenchymal stromal cells

Abstract

Ectogenic pancreatic islet transplantation has long been discussed as having the potential to reverse diabetes. The aim of the present study was to evaluate the therapeutic efficacy of co-transplantation with hypoxia pretreated mesenchymal stem cells (MSCs) and islets in a diabetic mouse model. MSCs were isolated from femoral and tibial bone marrow aspirates from female BALB/c donor mice. MSC proliferation rates and the expression levels of vascular endothelial growth factor A (VEGFA), interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1 and matrix metalloproteinase (MMP)-9 were measured in hypoxic conditions. Subsequently, a streptozotocin-induced diabetic model was established in BALB/c mice. Glucose tolerance and diabetes reversal rate following co-transplantation of hypoxia pre-cultured MSCs and islets were demonstrated at different conditions during transplantation. The present study results demonstrated that MSCs increased their proliferation rate and the secretion of growth-related cytokines, including VEGFA, IL-6, MCP-1 and MMP-9 in a hypoxic environment. In the diabetes animal model, fewer islets (~250) were required to reverse the impaired glucose tolerance condition in Islets + Hypoxia cultured MSCs transplant group compared with the Islets-only group (~400 islets) and the Islets + Normal cultured MSCs group (~300 islets). Hypoxia-cultured MSC co-transplantation accelerated glycemic utilization following glucose intake. In subjects with hyperglycemia control for islet only transplantation group, MSCs pre-cultured in hypoxic condition prior to co-transplantation may potentially improve islet tissue regeneration.