J Korean Soc Transplant.  2009 Dec;23(3):214-226. 10.4285/jkstn.2009.23.3.214.

Current Strategies for Successful Islet Xenotransplantation

Affiliations
  • 1Transplantation Research Institute, Seoul National University Medical Research Center, Seoul, Korea.
  • 2Transplantation Center Seoul National University Hospital, Transplantation Research Institute, Seoul National University Medical Research Center, Seoul, Korea.
  • 3Division of Nephrology, Transplantation Research Institute, Seoul National University Medical Research Center, Seoul, Korea. curie@snu.ac.kr

Abstract

Diabetes mellitus is increasing all over the world and is a serious health problem. Pancreatic islet transplantation is promising treatment for diabetes mellitus, but an imbalance between deceased pancreas donors and recipients limited the widespread clinical application. Therefore, pig islets could be used as an alternative islet source in transplantation. However, a big hurdle to clinical application of islet xenotransplantation is the instant blood mediated inflammatory reaction (IBMIR), which is characterized by activation of the coagulation cascade, platelets and complement systems. Innate immune cells infiltrate the islets in the process of IBMIR and thereby accelerate the early graft loss. Characteristics of IBMIR in islet xenotransplantion are very different from the rejection in solid organ xenotransplantation. Therefore, we focus on the molecules for surmounting IBMIR in order to accomplish successful islet xenotransplantation. To prevent the IBMIR in islet xenotransplantation, development of genetic modified pigs containing anti-coagulant, anti-thrombosis and complement regulatory genes, or capsulation of islet with biomaterials for blocking immune response around islet surface can be tried. Galpha-Gal knockout pigs and the diverse transgenic pigs for complement regulatory protein or anti-coagulant genes have been developed for xenotransplantation. This review summarized on characteristics of rejection in islet xenotransplantation and discusses the strategies for overcoming the rejection.

Keyword

Islet xenotransplantation; Instant blood mediated inflammatory reaction (IBMIR); Genetically modified pig; Diabetes mellitus
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