Islet xenotransplantation: progress towards a clinical therapy

Abstract

Purpose of review: The success of islet allotransplantation has highlighted the need for an alternative source of islet tissue. This review looks at the current status of islet xenotransplantation and what progress has been made towards a clinical therapy. Recent findings: There has been substantial progress in preclinical studies of islet xenotransplantation. Pig islets have been shown to control diabetes in rhesus macaques beyond 100 days using strong immunosuppression. There have been advances in our understanding of the fate of islets after transplantation. Exposure of pig islets to human blood leads to the instant blood-mediated inflammatory reaction, a likely cause of early graft loss. Islets surviving this reaction face immunological rejection by anti-pig antibodies and cell-mediated rejection. There has been progress with novel immunosuppressive approaches. The use of local immunosuppression secreted by the graft utilizes the therapeutic option of genetically altering the pig to enhance graft survival. Summary: Our understanding of issues such as instant blood-mediated inflammatory reaction and rejection have led to new strategies to overcome these problems. What is required now is well-planned preclinical studies to test these and to develop a protocol that is suitable to clinical application. © 2006 Lippincott Williams & Wilkins.