Adipose Tissue-Derived Mesenchymal Stem Cells Promote Angiogenesis and Prolong Graft Function in Pancreatic IsletTransplantation

Background and Aim: Although pancreatic islet transplantation has beensuggested as an alternative therapy for type 1 diabetes mellitus (T1DM),there are efficiency concerns that are attributed to poor engraftment oftransplanted islets. Avascular phase and the poor formation of bloodvessels in the late period lead to islet allograft loss which contributedto inefficiency and short-acting of islet transplantation. To overcome this limitation, in this study, we attempted to determine whether the inclusionof adipose tissue-derived mesenchymal stem cells (AT-MSCs) with islettransplantation could improve the graft function and neovascularization.Methods: Islets were transplanted, either alone or with an in vitroexpandedAT-MSCs, into an omental pouch in a rat model of streptozotocin(STZ)-induced diabetes. After transplantation, the grafted animals weremonitored every 5 days for their non-fasting blood glucose levels andchanges in body weight. In addition, at the end of the specified treatmentperiod (day 75), blood and omentum-bearing islet graft were collectedfrom different groups for biochemical and histological analysis in serumand tissue. Moreover, to test and evaluate the impact of transplantationof AT-MSCs on the in vivo vascularization of the islet grafts, we alsoassessed CD31 staining, a marker of endothelial cells.Results: Our results indicated that transplantation of 2000 islets onlyachieved normoglycemia with graft survival of > 50.5±14.15 days(mean±standard error of the mean), whereas that of 1000 allogeneicislets associated with the shorter islet graft survival (16.75±2.18 days).Interestingly, co-transplantation of 1000 islets with 6×106 AT-MSCs, withhalf of the required number of islets for successful islet transplantationalone, reversed diabetes and significantly prolonged graft survival(> 47.25±16.03 days) and resulted in an improvement of islet allograftoutcome similar to that of sole islet transplantation. Although, obtainedresults indicated the positive expression of CD31 in the grafts of bothtransplanted groups, a more pronounced CD31 staining was evident inthe rats transplanted with MSCs+islets (1000) as compared to the isletsalone (2000) transplanted rats, suggesting a potential role of AT-MSCs instimulating neovascularization.Conclusion: Therefore, our findings provide the evidence for theprotective action of AT-MSCs on islet survival and function through theimprovement of revascularization suggesting that AT-MSCs-assisted islettransplantation might be a better strategy for the treatment of T1DM,compared to the conventional method of islet transplantation.

Keywords:

Co-transplantation , Mesenchymal stem cells , Pancreatic islets , Type 1 diabetes mellitus , Vascularization