Abstract:
Objective To evaluate the efficacy of a combined immunosuppression regimen in modulating rejection in genetically modified pig-to-macaque xenogeneic heart transplantation.
Methods Two xenogeneic heart transplantation models were constructed using genetically modified pigs and macaques. Dynamic monitoring of recipient peripheral blood immune parameters and observation of graft pathological changes were performed.
Results Regimen 1, featuring B-cell depletion, T-cell inhibition, and C3 complement suppression, reduced lymphocyte levels but failed to control acute humoral rejection and macrophage infiltration. Regimen 2, adding C5 complement inhibition and interleukin -6 inhibition to Regimen 1, more effectively lowered lymphocyte levels, inhibited acute humoral rejection and complement activation, and decreased antibody deposition. However, a late-phase cytokine storm and residual T cells emerged.
Conclusions Regimen 2 reduces the hyperacute and acute rejection risks through multi-target intervention. Yet, it requires balancing medication complexity and safety. This indicates the need to optimize cellular immune regulation and adjust the plan through dynamic multidimensional monitoring.
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