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The combination of GTKO and expression of CD46 and/or CD55 has made hyperacute rejection a rarity in experimental organ xenotransplantation studies (46).
This ensures that hyperacute rejection will not occur.
Since the hyperacute rejection process is largely triggered by the sugar structures produced by gal transferase activity, Alexion believes that gal transferase knockout porcine cells will provide benefits that will be critical for achieving successful xenotransplantation.
Early Later Graft ischemia Rejection-acute and chronic Primary nonfunction Immunosuppressant side effects Hepatorenal syndrome Biliary stenosis Hepatopulmonary syndrome Disease recurrence Hepatic artery thrombosis Malignancy Immunosuppressant toxicity Hyperacute rejection Early acute rejection Portal vein thrombosis Infection and sepsis (a) (a) Can occur at any stage.
In past xenotransplants, surgeons could avoid hyperacute rejection by using organs from chimpanzees, the primate genetically most like humans.
An attempt to eliminate hyperacute rejection with human and baboon antibody in GalT-KO kidney has been tried (Diswall et al.
Four healthy piglets are born without the gene--alpha 1, 3 galactose- responsible for making an enzyme that adds sugar to the surface of pig cells that leads to hyperacute rejection of the pig organ.
Since complement activation following antigen-antibody binding is felt to be species-specific, organs from such animals, lacking in porcine complement-regulatory proteins, would upon anti-[alpha]-Gal-[alpha]1,3-Gal binding not activate complement and not undergo hyperacute rejection.
AVANT and its collaborators have conducted a series of animal experiments in which TP10 was successfully used to inhibit hyperacute rejection of pig hearts transplanted into cynomologus monkeys.
Although immediate hyperacute rejection of the transplanted organ has been overcome in animal experiments by multiple techniques, including eliminating the circulating natural antibodies, these antibodies eventually return and cause delayed organ rejection.