Islet transplantation is an established therapy for selected type 1 diabetes (T1D) patients with severe hypoglycemic unawareness and glycemic liability despite of insulin treatment. However, the donor organ is limited. Porcine islets are the best alternative source to overcome this limitation, and pig-to-nonhuman primate (NHP) naked islet xenotransplantation studies are being performed worldwide. Several studies including our own have presented successful proof-of-concept results based on immunosuppression regimen including the anti-CD154 monoclonal antibody. Particularly, long-term control of diabetes by adult porcine islet transplantation has been demonstrated in five consecutive monkeys, and the longest survival was ~1000 days after transplantation. Currently, pig-to-NHP islet xenotransplantation based on clinically applicable immunosuppression regimen is being pursued. In this chapter, we will describe all the procedures of pig-to-NHP naked islet xenotransplantation: (1) the porcine islet isolation from designated pathogen-free (DPF) miniature pigs, (2) diabetes induction in monkeys, (3) transplantation procedure via the portal vein, (4) immune monitoring comprising humoral and cellular immunity after porcine islet transplantation, and finally (5) liver biopsy and subsequent immunohistochemical procedure in detail.
Part of the book: Xenotransplantation