Porcine Islet Xenotransplantation for the Treatment of Type 1 Diabetes

Abstract

Type 1 diabetes is a disease that typically occurs in childhood and adolescence and has been estimated to account for 5% to 10% of all diagnosed cases of diabetes. It is caused by the destruction of beta cells in the islets of pancreas resulting in insulin deficiency that eventually leads to high glucose levels in the blood. If not properly treated, this condition can lead to long-term secondary complications of diabetes such as kidney disease, heart disease, and blindness. Individuals with type 1 diabetes require insulin injections for survival, but insulin injection never achieves perfect regulation of glucose in the blood and secondary complications of diabetes still develop. An attractive alternative treatment for type 1 diabetes is the replacement of islets by transplantation. Islet transplantation offers a physiological means of delivering insulin thus has the potential to control better the levels of glucose in the blood. With an islet transplant, the beta cells that have been destroyed are replaced by new beta cells in the islets, which are able to sense the changes in blood glucose levels. The very first attempts at islet transplantation occurred prior to the discovery of insulin in 1922 (Banting & Best, 1922) when Von Mering and Minkowski demonstrated in 1889 that the pancreas was responsible for the regulation of blood glucose as removal of the pancreas made the dogs diabetic (von Mering, 1889). Minkowski subsequently attempted to reverse diabetes in the diabetic dogs by auto-transplanting fragments of pancreas under the skin but his attempt failed (Minkowski, 1892). Subsequent advances in rodent models established the foundation for techniques used in current day islet transplantation. In 1989, the Islet Transplant Group at the University of Alberta carried out Canada’s first islet transplant (Warnock et al., 1989). Long-term insulin independence was achieved when a combination of freshly isolated and cryopreserved islets were used (Warnock et al., 1992). Up to 1999, of the 267 islet allografts transplanted worldwide, only 12.4% have resulted in insulin independence for periods of more than 1 week, and only 8.2% have done so for periods of more than 1 year (Brendel et al., 1999). Despite these sobering long-term results, compared with intensive exogenous insulin therapy, islet transplantation provided superior metabolic control, prevented hypoglycemic events and held the potential to decrease secondary complications of diabetes (Alejandro et al., 1997) a substantial impetus to encourage continued support of the field. Islet transplantation, however, faces a number of challenges, including a shortage of suitable human donors for transplantation and the required long-