Enzymatic remodelling of the carbohydrate surface of a xenogenic cell substantially reduces human an
Author: ["Mauro S. Sandrin","William L. Fodor","Effie Mouthtouris","Narin Osman","Shlomo Cohney","Scott A. Rollins","Edward R. Guilmette","Eva Setter","Stephen P. Squinto","Ian F.C. Mckenzie"]
Publication: Nature Medicine
CITE.CC academic search helps you expand the influence of your papers.
Abstract
The major obstacle to successful discordant xenotransplantation is the phenomenon of hyperacute rejection (HAR). In the pig-to-primate discordant transplant setting, HAR results from the deposition of high-titre anti-α-galactosyl antibodies and complement activation leading to endothelial cell destruction and rapid graft failure. To overcome HAR, we developed an enzymatic carbohydrate remodelling strategy designed to replace expression of the Galα-1,3-Gal xenoepitope on the surface of porcine cells with the non-antigenic universal donor human blood group O antigen, the α-1,2-fucosyl lactosamine moiety (H-epitope). Xenogenic cells expressing the human α-1,2-fucosyltransferase expressed high levels of the H-epitope and significantly reduced Galα-1,3-Cal expression. As a result, these cells were shown to be resistant to human natural antibody binding and complement-mediated cytolysis.
Cite this article
Sandrin, M., Fodor, W., Mouthtouris, E. et al. Enzymatic remodelling of the carbohydrate surface of a xenogenic cell substantially reduces human antibody binding and complement-mediated cytolysis. Nat Med 1, 1261–1267 (1995). https://doi.org/10.1038/nm1295-1261
