Clinical islet transplantation: where immunity and metabolism intersect?

Abstract

Purpose of review: The dramatic results of the Edmonton Protocol in 2000 triggered tremendous excitement over the application of pancreatic islet transplantation as a viable approach to achieving consistent insulin independence in type 1 diabetic patients. However, this optimism in the field was tempered by follow-up studies showing frequent attrition of graft function commonly requiring a return to exogenous insulin therapy within 1-3 years after transplant. The purpose of this review is to put these initial studies in perspective and to highlight progress and challenges in this important field.

Recent findings: Recent clinical and experimental findings demonstrate a progressive improvement in the function and durability of islet allografts. Induction therapies targeting T lymphocytes and costimulatory pathways have been highly effective at promoting islet transplant function. It is also apparent that islet injury associated with metabolic distress provides a nonimmune barrier to islet transplant outcomes.

Summary: Newer therapeutic interventions show great promise for attenuating the adaptive immune response to islet allografts. Also, clarifying the mechanisms of metabolic-related tissue distress may provide additional potential targets for improving islet graft outcomes.