Introduction: With advancements in xenotransplantation, genetically edited pigs are being explored as potential organ donors for primates. This study aims to discuss the immunosuppressive regimen used in the xenotopic heart transplantation from a gene-edited pig to a rhesus macaque, with the goal of providing reference for future studies.
Methods: A comprehensive immunosuppressive protocol was employed, including preoperative induction therapy (anti-CD20 antibody - rituximab, anti-CD154 monoclonal antibody, antithymocyte globulin, cobra venom factor, methylprednisolone) initiated 14 days before surgery, and postoperative maintenance therapy (anti-CD154 monoclonal antibody, mycophenolate mofetil, methylprednisolone). The recipient's immune status was monitored using flow cytometry and blood cell counts to evaluate the efficacy of the immunosuppression.
Results: The rhesus macaque survived 46 days post-transplant with stable function of the transplanted heart and no signs of hyperacute or acute rejection. The induction therapy effectively reduced the numbers and proportions of lymphocytes, B cells, and T cells, maintaining low levels of immune activity. Postoperative monitoring indicated controlled complement cytotoxicity (3.4%–5.1%), stable IgG and IgM antibody binding, and favorable absolute values and ratios of B/T lymphocytes. Pathological analysis showed minor myocardial damage in the monkey heart but more severe damage in the porcine heart, suggesting chronic immune rejection.
Conclusion: The immunosuppressive regimen demonstrated significant effectiveness in suppressing hyperacute and acute rejection, providing an important strategy for xenotransplantation of gene-edited pig hearts. However, observed chronic rejection highlights the need for further optimization of immunosuppressive protocols, particularly for managing chronic rejection.