Gal knockout and beyond.
Recently, Galalpha1-3Galbeta1-4GlcNAc (Gal) knockout (k/o) pigs have been developed using genetic cloning technologies. This remarkable achievement has generated great enthusiasm in xenotransplantation studies. This review summarizes the current status of nonhuman primate experiments using Gal k/o pig organs. Briefly, when Gal k/o pig organs are transplanted into primates, hyperacute rejection does not occur. Although graft survival has been prolonged up to a few months in some cases, the overall results were not better than those using Gal-positive pig organs with human complement regulatory protein transgenes. Gal k/o pig kidneys rapidly developed rejection which was associated with increased anti-non-Gal antibodies. Although the precise mechanisms of Gal k/o pig organ rejection are not clear, it could result from incomplete deletion of Gal, up-regulation of new antigen (non-Gal antigen) and/or production of non-Gal antibodies. Future work in xenotransplantation should place emphasis on further modification of donors, such as combining human complement regulatory genes with Gal k/o, deleting non-Gal antigens and adding protective/surviving genes or a gene that inhibits coagulation. Induction of donor-specific T- and B-cell tolerance and promotion of accommodation are also warranted.
Zhong
R
R
Department of Surgery, University of Western Ontario, Multi-Organ Transplant Program, London Health Sciences Centre, Transplantation Group, Robarts Research Institute, London, Ontario, Canada.
D000818:Animals; D030801:Animals, Genetically Modified; D005690:Galactose / Q000172:deficiency* / Q000276:immunology*; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control; D011323:Primates; D013552:Swine; D014183:Transplantation, Heterologous / Q000009:adverse effects / Q000379:methods / Q000639:trends
D005690:Galactose