NEXT · Nano Engineering for Cross Tolerance: new approach for bioengineered, vascularised, chimeric islet transplantation in non-immunosuppressed hosts

Diabetes is caused by insufficient or lack of insulin secretion by the specialized B cells of the pancreas and, if not treated adequately evolves into in complications which alter patients integrity and wellness. Treatment is based on lifetime drugs administration for blood glucose control or parenteral infusion of insulin to better control glucose levels and glycosylation of hemoglobin. Artificial pancreases are in development but still dependent by external energy sources and need permanent transcutaneous access to release the hormone. Pancreatic whole organ transplantation is a major intervention requiring selected recipient and matched cadaveric donor which keep numbers down. Islet of Langerhans transplantation is a non-invasive method for the treatment of type 1 diabetes but several questions remain and several issues have to be addressed in order to improve the method since islet engraftment is clearly suboptimal, as a result of pro-apoptotic and pro-inflammatory stimuli sustained during islet isolation and at the site of implantation, the long-term islet graft function drops to 15% with time, and the current systemic immunosuppressive regimen has several drawbacks in terms of side effects. Solution should be find to increase transplantation efficiency with an higher number of islet, eventually from animals, induce tolerance toward the graft, avoiding systemic, lifetime immunosuppression and, lowering a specific inflammatory reaction and enhancing graft micro vasculogenesis to improve islet nesting. NEXT provides a 360° solution to the pitfalls of current methodology for pancreatic islet transplantation: i) Nano technologies, to engineer donor cell surfaces in order to derange recognition and suppress their rejection; ii) Advanced tissue engineering methods, to assemble bio synthetic islet, enriched by chimeric microvasculature; iii) Innovative double immune-suppressive strategy by graft - bound immunosuppressive nano peptides and shielded by self- vasculature