Novel Replaceable Device Encapsulating Porcine Islets Enable Long-Term Discordant Xenotransplantation in Immunocompetent Diabetic Mice

Islet transplantation is an effective treatment for type 1 diabetes (T1D). However, a shortage of donors and the need for immunosuppressants are major issues. The ideal solution is to develop a source of insulin-secreting cells and an immunoprotective method. No bioartificial pancreas (BAP) devices currently meet all of the functions of long-term glycemic control, islet survival, immunoprotection, discordant xenotransplantation feasibility, and biocompatibility. A novel device was developed, in which porcine islets were encapsulated in a highly stable and permeable hydrogel and a biocompatible immunoisolation membrane. Discordant xenotransplantation of the device into diabetic mice improved glycemic control for more than 200 days. Glycemic control in new diabetic mice "relay-transplanted" with the device once retrieved was also improved. The easily retrieved devices with almost no adhesion or fibrosis showed sustained insulin secretion even after the two xenotransplantations. This device has the potential to be a useful BAP for the treatment of T1D.