Therapeutic potential of mesenchymal stem cells co-transplantedwith pancreatic islets for the treatment of type-1diabetes

Treatment of type-1diabetes with pancreatic islet transplantation is an innovative therapeutic approach, but itsclinical application is still very limited, mainly for the great number of islets necessary and for their short survival. An intriguing means to improve the performance of pancreatic islets transplantation may be represented by Mesenchymal Stem Cells (MSCs), adult stem cells already known to support the survivalof different cellular populations. In this work we investigated the ability of Mesenchymal Stem Cells (MSCs) to reduce the number of pancreatic islets necessary to achieve glycaemic control in Streptozotocin-induced diabetic rats, and their effect ona long term disease complication,the diabetic neuropathy. Diabetic rats showed high blood glucose level and important neuropathic signs, such as the decrease of Nerve Conduction Velocity (NCV) and the impairment of nociceptive (thermal and mechanical) thresholds. Two months after transplantation, diabetic rats co-transplanted with MSCs and a suboptimal number of pancreatic islets showed a marked and significant glycaemia value reduction, an improvement of thermal and mechanical sensitivity, and a nearly complete restoration of NCV with respect to diabetic-untreatedrats. The in vitro analysis of the putative mechanisms of MSC positive action on pancreatic islets suggested the involvement of both trophic soluble factors released by MSCs, and their differentiation into insulin-releasing cells after the direct contact with pancreatic islets. In conclusion, we demonstrated that co-transplantation with MSCs reduces the number of pancreatic islets needed to reach glycaemic control, and inducesthe regression of painful neuropathy signs, thus ameliorating diabetes complicationsmanagement.