Towards curing type 1 diabetes: Prospects and challenges of allogeneic or xenogeneic donor islet cell transplantation

Abstract

Type 1 diabetes (T1D) is a chronic, lifelong, autoimmune disease that is debilitating and life-threatening to those who suffer from severe hypoglycaemic events or the devastating chronic complications. Exogenous insulin replacement, including the artificial pancreas, is the current mainstay of T1D therapy but cannot prevent the chronic vascular complications of the disease. They are also responsible for contributing to severe iatrogenic hypoglycaemia and impaired hypoglycaemic awareness. β-cell replacement with either pancreas or islet allotransplantation can reverse diabetes leading to better glycaemic control, prevention of hypoglycaemic events and improved quality of life for patients. The limited supply of cadaveric organ donors is a major barrier to this therapeutic option. Thus, alternative sources of islets are being actively explored, mainly human pluripotent stem-cell derived islets and xenogeneic porcine islets. Although these sources harbor their own risks and problems, various novel and innovative solutions are being perseveringly investigated across the globe to overcome these in the hopes that safe islet transplantation may one day be available to all T1D patients suffering from severe hypoglycaemic events. This review will concentrate on pre-clinical and clinical studies, in addition to the latest scientific discoveries relevant to T1D transplantation therapy using allogeneic or xenogeneic donor islet cells.