Characterization of Mesenchymal Stem Cells effect on Pancreatic Islets: a tool for Type 1 Diabetes Therapy

Diabetes Type 1 is a metabolic syndrome characterized by a progressive degeneration of β-cells, due to an autoimmune mechanism; it follows that diabetic patients show low insulin level and consequently they need for an insulin replacement therapy. Even if in the last decades many improvements have been made especially from the pharmacological point of view, new strategies have been investigated, in order to improve glycemic control; among these, a very promising approach is represented by pancreatic islet transplantation. Compared to whole pancreas transplantation, this approach is more minimally invasive and even a milder immunosuppressive regimen is needed. The clinical use is however limited by the large number of islets needed for the transplant and by their short survival after transplantation, so new approaches have been proposed; one of these is the use of Mesenchymal Stem Cells (MSCs); MSCs have been proposed for the management of many degenerative diseases for their immune-modulatory, differentiation and survival-supporting properties. Aim of this study was to investigate the putative positive effect of MSCs on pancreatic islets in vitro, and to verify the actual improvement in diabetes animal model. We set up direct and indirect co-cultures to analyzed the role of soluble factors and mixed co-cultures in which both previous conditions coexisted. We observed that MSCs can prolong islet survival by soluble factors, while when directly co-cultured with MSCs changed their expression profile and differentiated in insulin-releasing cells. In mixed co-cultures both the results were present therefore we moved to in vivo models to verify the effect of mixed co-cultures. In our model, diabetes was induced in rats by streptozotocin i.p. injection. The animals were divided into five groups: healthy rats; diabetic rats; diabetic rats transplanted with pancreatic islets; diabetic rats transplanted with pancreatic islets and MSCs; diabetic rats transplanted only with MSCs. As reported in literature, 2,000 pancreatic islets transplanted alone, in diabetic rats, were not able to improve clinical case. For this reason we decided to transplant 3,000 islets alone, while only 2,000 if co-transplanted with MSCs. In both these groups we observed an improvement of clinical case, indeed a good glycemic profile was reached and behavioral test confirmed the positive effect of transplants. Moreover we can assert that very similar results were obtained from the group receiving 3,000 islets alone and those receiving only 2,000 pancreatic islets and 1,000,000 MSCs, indicating that MSCs were able to support pancreatic islets survival and functionality. These data are very promising and made the co-transplantation of pancreatic islets and MSCs a concrete alternative approach for Type 1 Diabetes therapy, however further studies may clarify all molecular aspects involved in MSC positive effect on pancreatic islets.