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 (IL)-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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