Molecular remodeling of complement regulatory proteins for xenotransplantation

In pig-to-human discordant xenotransplantation, human complement is a major barrier against long survival of xenografts. Human complement regulatory proteins expressed on xenografts have been adapted as safeguards against host-induced hyperacute rejection of xenografts. For successful xenotransplantation, there have been many attempts to generate molecules with potent human complement regulatory activity but without activities related to harmful functions such as infection, immunosuppression and signal transduction devastating cellular homeostasis. Here, we summarize the strategy by which molecules for xenotransplantation should be designed and propose a GPI-anchored form of monomeric human C4bp as a candidate for efficient protection of swine xenografts from human complement attack.