Islet surface PEGylation attenuate the instant blood-mediated inflammatory reaction in intrahepatic islet transplantation

Abstract

Clinically intrahepatic pancreatic islet transplantation is carried out for patients suffering from type 1 diabetes mellitus but the instant blood mediated inflammatory reaction (IBMIR) initiated from platelet adhesion onto the islet can impair the islet function. Previously, chemically modified islets were developed with a protective poly(ethylene glycol) (PEG) polymer, which could repel adhering platelets in the blood stream owing to its biocompatible properties. The results show that PEG-based chemical modification can prevent the adhesion of platelets in the tubing loop model in vitro. Moreover, this islet PEGylation strategy appears to avoid the islet cytotoxicity associated with the further recruitment of leukocytes and monocytes via an interaction with platelets, thereby showing normal viability and function of insulin secretion of the PEGylated islets. In addition, when transplanted into the liver via the portal vein, the PEGylated islets could still normally function for insulin secretion without binding onto the islet surface with platelets and/or leukocytes. On the other hand, the surface of unmodified islets (control) was bound severely with platelets and leukocytes in vitro and in vivo, thereby affecting the viability and functionality of the islets. These results strongly suggest that an islet PEGylation remedy can provide an effective clinical means of attenuating IBMIR after intrahepatic islet transplantation.

Pig-to-Monkey Islet Xenotransplantation Using Multi-Transgenic Pigs

“…Islets from genetically unmodified pigs can normalize blood glucose levels in diabetic monkeys , but intensive immunosuppressive therapy is required to protect the islets from rejection. An additional hurdle is the islet graft loss that occurs immediately after intravascular islet infusion, which involves activation of coagulation, complement and inflammatory mediators, events that have been characterized as IBMIR . The advent of GE pigs renders donor tissue more compatible to the recipients .…”