Seven Years of Experiences of Preclinical Experiments of Xeno-Heart Transplantation of Pig to Non-Human Primate (Cynomolgus Monkey)

Abstract

BackgroundThe absolute shortage of donors compared with patients requiring transplantation is currently an unsolved problem, and the only possible solution may be xenotransplantation. To establish a successful clinical trial, a preclinical study using nonhuman primates is essential. Starting in November 2011, our team initiated heterotopic abdominal heart xenotransplantation, the first in the Republic of Korea. We present here the initial 7-year results. MethodsA total of 22 xenotransplantation procedures have been performed since 2011. Single transgenic pig (alpha-galactosidase transferase knockout [GalT KO], n = 16), double transgenic pig (GalT KO + CD46, n = 3, and GalT KO + CD39, n = 2), and triple transgenic pig (GalT KO + CD46 + CD70, n = 1) models were used. Our baseline regimen of immunosuppressants comprised CD154 ab, rituximab, anti-thymocyte globulin, tacrolimus, mycophenolate mofetil, and steroids. ResultsThe mean graft survival was 16 ± 16.27 days, and the mean graft survival was significantly longer in cases performed since 2014 (7.5 ± 8.03 days vs 24.67 ± 17.50; P = .01). Although the donor heart ischemic time was decreased per annum, no correlations could be found between ischemic time and survival days of the graft. Double or triple genetic manipulated hearts exhibited significantly better survival (11.63 ± 11.29 days vs 30.83 ± 20.34 days; P = .03). When the ratio of heart weight (grams) to nonhuman primate weight (kilograms) was lower, the results tended to be better (P < .05). The rate of immediate postoperative bleeding (9%, n = 2) causing death was relatively high in the earlier period, but there have been no serious surgical complications affecting graft survival since 2013. ConclusionsInvestigation of effective and optimal target genes for each organ to further progression toward better results is important. In addition, the immunosuppressive regimen needs to be further studied and constantly refined.