In vitro characteristics and in vivo outcome of α1,3-galactosyltransferase gene-knockout miniature pig cornea in full-thickness corneal xenotransplantation using nonhuman primate

Abstract

Abstract We investigated the biofunctional profiles of α1, 3-galactosyltransferase gene knockout (GTKO) miniature pig cornea and its outcome in pig-to-rhesus full thickness corneal xenotransplantation (FTCX). Ten eyes of GTKO miniature pigs (n = 5) were evaluated for biofunctional characteristics. Five Chinese rhesus macaques underwent FTCX (mean donor age: 11.3 mo). Systemic tacrolimus, basiliximab, and IVIG were administered as programmed schedules. T cell subsets, antibodies (Ab) in blood, and C3a in aqueous humor (AH) were evaluated. The results were compared with those of the wild type miniature pig corneal grafted group (n = 4, all grafts survived > 24 weeks, using anti-CD154 Ab) as controls. Mean central corneal thickness was 763 μm. Na+/K+ ATPase was well expressed 7 days after preservation. Mean endothelial cell density was 4729/mm2, and was maintained >2800/mm2 through 7 days. Mean doubling time was 30.4 hour which was comparable to that in SNU miniature pigs (30.7 hour, p = .413). Median graft survival was 72 days. Regulatory T cells at rejection decreased from baseline (p = .043) and were lower than those of controls at postoperative (postop) 24 weeks (p = .014), however the other T cell subsets did not change. At rejection, anti-non-αGal Ab increased from baseline (p = .043), however Anti-αGal Ab did not. C3a in AH at postop 4 weeks and at rejection increased from baseline (all p = .043). At postop 4 weeks, AH and plasma C3a were higher than those of controls (p = .016 and .036, respectively). The biofunctional characteristics of GTKO miniature pig cornea are feasible for FTCX. Rejection of GTKO pig-to-rhesus FTCX is related with non-αGal Ab, complement and decrease of regulatory T cells. Addition of B cell suppressing regimen should be considered.