Hyperacute rejection is attenuated in GalT knockout swine lungs perfused ex vivo with human blood

Alpha1,3-galactosyltransferase knockout does not alter the properties of porcine extracellular matrix bioscaffolds

“…Inactivation of both alleles of GGTA1 results in an inactive GT enzyme and therefore these pigs lack aGal epitopes. The aGal(À) porcine organs, such as the heart, survived up to 6 months in nonhuman primates, proving the effectiveness of the technique [43][44][45]. The ECM bioscaffolds derived from these aGal(À) pigs were deficient in the aGal epitopes, which was verified in our preliminary studies [29].…”

Beyond Antibody-Mediated Rejection: Hyperacute Lung Rejection as a Paradigm for Dysregulated Inflammation

“…parallel development of nuclear transfer ("cloning") technology for use in pigs [40,41]. Recent availability of homozygous galactosyl transferase knock-out (GalT-KO) pigs allowed initial assessment of the role of non-Gal xenoreactive antibodies, complement, and coagulation to prevent HAR and DXR of hearts and kidneys in baboons [42]. Work by others confirmed that endothelial and parenchymal cells from GalT KO animals do not express the Galα1-3-Gal epitope [40,41].…”

Molecular regulation of xenoreactivity

“…Other factors, particularly pulmonary intravascular macrophages [13 ] and the anaphylotoxin C5a [14], appear to be the critical mediators of early injury and rejection. Intriguingly, however, Gal KO pig lungs functioned for an average of 2 hours when perfused ex vivo with human blood, compared with less than 5 minutes for wild type lungs [15]. The importance of Gal in the rejection of pulmonary xenografts will remain unclear until the appropriate pigto-baboon experiments have been performed.…”