Comparison of Gal and Non-Gal-Mediated Cardiac Xenograft Rejection

Abstract

The histology of rejection seemed independent of the anti-Gal or non-Gal immune response. Myocyte vacuolization seems to be an early feature of delayed xenograft rejection presaging more classic pathologic features.

Genetically engineered pigs and target-specific immunomodulation provide significant graft survival and hope for clinical cardiac xenotransplantation

“…However, there are parts of this puzzle that still need to be solved (10, 11). Some of the major obstacles, after overcoming the Gal antibody barrier, include the presence of preformed and elicited non Gal antibodies against multiple antigens (12), consumptive coagulopathy (CC) caused by rapid depletion of platelets (13), and TM due to an induced hypercoagulable state (14). …”

One-Year Heterotopic Cardiac Xenograft Survival in a Pig to Baboon Model

“…All previous reported graft survivals were at least 4 months less (1, 2). Antibodies, both preformed and elicited against various xenoantigens, that mediate graft rejection (3) and thrombotic microangiopathy or consumptive coagulopathy due to platelet activation (4), have been the main obstacles to successful xenograft survival. In this study both these mechanisms were efficiently controlled in all 5 baboons by altering the genes of the donor pig and recipient treatment with a regimen that includes anti CD40 antibody.…”

Immunological Challenges and Therapies in Xenotransplantation

“…Judging from the data obtained so far, however, pig xenografts expressing CRPs are not protected from the overwhelming complement activation occurring in AHXR, even if CRPs are expressed on a GalT-KO background. This underlines the existing limitation of the use of CRP transgenic organs (Le Bas-Bernardet et al 2011;Tazelaar et al 2011). Indeed, it may be necessary to implement a multistep inhibition of the complement cascade, associated with a tight regulation of the coagulation system involved in complement activation (Huber-Lang et al 2006).…”