Islet xenotransplantation: An update on recent advances and future prospects

Abstract

Type 1 diabetes (T1D) is an autoimmune disorder characterized by pancreatic β cell destruction, leading to a gradual loss of endogenous insulin secretion and ensuing hyperglycemia. Current treatment methods for T1D include the administration of exogenous insulin or the replacement of β-cell mass through either pancreas or islet transplantation. Current β-cell replacement trials have reported a lower incidence of potentially fatal hypoglycemic episodes when compared to exogenous insulin therapy. Islet allotransplants have also shown success in establishing insulin independence during the first year post transplant; however, transplant recipients progressively become increasingly dependent on insulin, and this therapy has been limited to a selected pool of patients due to a shortage of islet donors. The outcomes of the procedure have also been inconsistent, with the most success coming from highly experienced transplant centers. Due to these inherent limitations of islet allotransplantation, xenotransplantation has been investigated as a possible alternative, since there are several potential advantages. Xenotransplantation has the potential of offering a reliable and consistent supply of islets. Having a readily available source of islets provides a significant advantage of being able to schedule the transplant procedure in advance. This is of great importance since most immunosuppression induction strategies require pre-dosing patients before the procedure. In addition, the development of specific pathogen–free (SPF) and designated disease pathogen-free (DPF) facilities and the propagation of animals with limited or no transmissible zoonotic diseases make xenotransplantation the treatment of choice for T1D patients. This chapter aims to provide a comprehensive review of islet xenotransplantation for the treatment of type 1 diabetes, including a historical review, problems faced by xenotransplantation, current research on xenotransplantation outcomes and clinical trials, and future developments.