Improvement of survival and insulin function of islet grafts in diabetic rats by co-transplantation of adipose tissue-derived mesenchymal stem cells

Pancreatic islet transplantation is a commonly therapeutic strategy for type 1 diabetes mellitus (T1DM). However, it has been hindered by the shortage of available donor organs, that spurs research into alternative means of β-cells from stem cells. Recent reports have demonstrated that co-culture and co-transplantation of pancreatic islets with stem cells, preserve and improve islet mass and quality by increasing islet function in vitro and greater graft viability, function and longevity in vivo, suggesting possibilities for relevant clinical trials to be carried out. On such a basis, this study was designed to determine the effects of hybrid islet transplantation with adipose tissue-derived mesenchymal stem cells (AT-MSCs) on the survival and insulin function of allogeneic islet graft in a diabetic rat. Different numbers of islets either alone or with AT-MSCs were transplanted simultaneously into omental pouch in a rat model of streptozotocin (STZ)-induced diabetes. Our findings provide evidence that AT-MSCs are suitable for creating a microenvironment favorable for the repair and longevity of pancreatic islet β-cells, exerting their effects through various mechanisms including: i) contribution to insulin production through a differentiation-associated process; ii) preservation of islet morphology; iii) restoration of islet function; iv) secretion of anti-inflammatory and immunoregulatory factors (cytokines); v) enhancement of islet revascularization. In conclusion, we propose that AT-MSCs as a secondary cell source may be best used in both islet co-culture and co-transplantation strategies to limit the mass of donor islet materials, which currently delimitates the broader application of allogenic islet transplantation as a therapy for T1DM

کلیدواژه ها:

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