Current Concepts of Using Pigs as a Source for Beta-Cell Replacement Therapy of Type 1 Diabetes

Abstract

The global prevalence of insulin-dependent diabetes mellitus is rapidly increasing. In spite of major improvements in insulin treatment regimens and diabetes technology (e.g., artificial pancreas devices), glucose control remains problematic in a substantial proportion of diabetic patients. Those patients may benefit from beta-cell replacement therapies. Allotransplantation of pancreas or isolated pancreatic islets is limited by the small number of organ donors. Thus, alternative sources of beta-cells are being developed and tested. These include endocrine progenitor cells or mature beta-cells derived from pluripotent human stem cells and attempts to derive human pancreas tissue in animal hosts by interspecific chimeric complementation experiments. Xenotransplantation of porcine islets is a realistic alternative option. Immune rejection of xenoislets can be prevented by immunosuppression of the recipient or by encapsulation of the islets in microdevices or macrodevices. Using precise and efficient genetic engineering of donor pigs, immune-protected xenoislets with improved functionality can be generated.