Current situation of clinical islet transplantation from allogeneic toward xenogeneic

Currently, type 1 diabetes requires lifelong insulin injection and careful blood glucose control to prevent secondary complications, but islet transplantation could make a type 1 diabetic patient insulin independent. On the other hand, islet transplantation needs human donors and donor shortage is the most serious issue. To alleviate the donor shortage, non-heart-beating and living donors were used; in addition, the efficacy of islet isolation and transplantation has been improved. However, the donor shortage issue will not be solved as long as human donors are the only source. To solve the donor shortage issue, islet xenotransplantation using porcine islets was initiated in 1994. Islet xenotransplantation has a potential to cure many type 1 diabetic patients, although there is the risk of developing serious or novel infection. Therefore, the World Health Organization has been interested in xenotransplantation, and the International Xenotransplantation Association (IXA) has published consensus statements to initiate xenogeneic islet transplantation. Clinical islet xenotransplantation was conducted under the official regulation, and safety and efficacy data have been accumulated. Currently an efficient method to overcome xenorejection is an important research target. In addition to traditional immunosuppressive drugs and immune isolation methods, the gene modification with CRISPR and blastocyst complementation have been investigated with promising outcomes. Once the xenorejection issue is overcome, islet xenotransplantation should become a curative treatment for type 1 diabetic patients. Highlights Allogeneic islet transplantation has been developed for unstable type 1 diabetic patients to stabilize the blood glucose levels and prevent hypoglycemia, and donor shortage is the most serious issue. To alleviate the donor shortage issue, non-heart-beating donor and living donors were used and to solve the donor shortage issue porcine islets have been used for islet transplantation. Recent new technologies including CRISPR and blastocyst complementation should improve the efficacy of islet xenotransplantation.