Achieving and maintaining insulin independence in human islet transplant recipients

Abstract

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 co-transplanted/engrafted islet precursor cells.