Achieving and maintaining insulin independence in human islet transplant recipients

For islet transplants to complete the transition from clinical research to clinical care restoration of insulin independence must be achieved-as with pancreas transplants-with a single donor. To achieve this critical milestone more consistently it will be imperative to pursue the following complementary strategies simultaneously: 1) enhancing the metabolic potency, inflammatory resilience, and immune stealth of isolated islets; 2) inhibiting the thrombotic and inflammatory responses to transplanted islets; and 3) achieving immune protection with strategies lacking diabetogenic side effects. Maintaining insulin independence will be a different challenge requiring us to clarify whether failure of initially successful islet allografts in type 1 diabetes is related: to 1) failure of immunosuppressive regimens to control alloimmunity and autoimmunity; 2) failure of islet regeneration in the presence of currently applied immunosuppressive regimens; and/or 3) failure of islet neogenesis in the absence of an adequate mass and viability of cotransplanted/ engrafted islet precursor cells.