TY  - JOUR
AU  - Shimoda, Masayuki
AU  - Matsumoto, Shinichi
PY  - 2018
DA  - 2018/04/25
TI  - Islet Xenotransplantation for the Treatment of Type 1 Diabetes
JO  - OBM Transplantation
SP  - 008
VL  - 02
IS  - 02
AB  - Allogeneic islet transplantation has been established to prevent severe hypoglycemia for unstable type 1 diabetic patients. Recent phase 3 clinical trial clearly demonstrated the benefit of allogeneic islet transplantation. Severe hypoglycemia is serious issue not only for type 1 diabetic patients but also type 2 diabetic patients especially aged patients. Considering the possible demands for such patients, donor shortage will be the serious issue. To solve this issue, islet xenotransplantation using porcine islets is a promising remedy. There are several advantages of porcine islets comparing with human islets including unlimited and on demand supplies, higher quality of islets from healthy donor, safer with designated pathogen free (DPF) donor pigs and possible gene modifications. Comparing ES and iPS derived islets, porcine islets have more profound clinical experiences with evidences of safety and efficacy since 1990s. In addition, promising outcomes were published using porcine islets to restore normoglycemia in the non-human primate diabetes models. One of the major concerns of islet xenotransplantation is zoonotic infections. To prevent this possible complication, using DPF status donor pigs, and monitoring porcine endogenous retrovirus (PERV) are key elements. In addition, compliance with regulatory rule is critically important to prevent spreading the zoonotic infections. Recently, international xenotransplantation association updated their consensus statements to promote islet xenotransplantation and it emphasized the importance of the regulatory compliance. In 2014, a clinical trial of encapsulated porcine islet xenotransplantation for the treatment of type 1 diabetes under comprehensive regulation was published. This study demonstrated the safety of islet xenotransplantation and some efficacy. Recently, it was published the encapsulated porcine islet xenotransplantation provided clinical benefit for type 1 diabetic patients. Encapsulated porcine islet xenotransplantation seems promising, and several groups have demonstrated improved capsules which may solve the fibrosis issue of capsules. CRISPR/CAS9 system makes the gene editing technology stable and easy. In fact, it was demonstrated that PERVs were completely eliminated with CRISPR technology. Human compatible pig will be made with this technology. Eventually, human pancreas will be created in pig body with blastocyst complementation technology. These aggressive scientific advances will bring islet xenotransplantation as a standard therapy for diabetic patients.
SN  - 2577-5820
UR  - https://doi.org/10.21926/obm.transplant.1802008
DO  - 10.21926/obm.transplant.1802008
ID  - Shimoda2018
ER  -