Xenograft rejection--molecular mechanisms and therapeutic implications

The rejection of a vascularized xenograft between phylogenetically distant species is a result of natural antibody binding to the graft endothelium and the activation of complement. The subsequent dysfunction of endothelial cell physiology results in the loss of vascular integrity and ultimately the failure of the graft. Strategies aimed at preventing the initial steps of antibody binding and complement activation have successfully prevented hyperacute rejection in experimental models resulting in a significant prolongation of xenograft survival. The rapidly increasing understanding of the mechanisms of xenograft rejection, and the potential ability to counter these mechanisms using recent advances in molecular biology, immunology, and vascular biology, provide encouragement that discordant xenotransplantation may prove clinically applicable.