Islet transplantation-immunological challenges and current perspectives

Core Tip

Core Tip: Type 1 diabetes (T1D) is associated with loss of beta-cell mass and insulin secretion. Regardless of its nature, autoimmune or idiopathic, the loss of own insulin secretion is a hallmark dysfunction in T1D mellitus; thus, therapeutic options are aimed at either replacing the missing insulin or restoring physiological insulin secretion to achieve normoglycemia and postponing micro- and macrovascular complications. Nevertheless, the need to completely replace the depleted pancreatic secretion also leads to the emergence of new therapeutic horizons, including pancreas and islet cell transplantation. However, this approach also meets several immunological challenges-cellular and antibody-mediated rejection and loss of function. To improve the outcomes, several approaches are performed: Immunosuppression, apoptotic donor lymphocytes, anti-TIM-1 antibodies, mixed chimerism-based tolerance induction, induction of antigen-specific tolerance utilizing ethylene carbodiimide-fixed splenocytes, infusion of donor apoptotic cells before transplantation, combined with anti-CD40L antibodies and rapamycin, preconditioning of isolated islets, inducing local immunotolerance, cell encapsulation and immunoisolation, using of biomaterials, immunomodulatory cells, etc. mesenchymal stem cells, as an adjunct therapy to islet transplantation, can promote long-term graft survival, possibly by reducing inflammation and enhancing immune tolerance.