Bai Le, Dai Ziqiang, Ren Zhipeng, et al. Dynamic analysis of immune responses in heterotopic heart transplantation model of genetically modified pig-to-macaque[J]. ORGAN TRANSPLANTATION. DOI: 10.12464/j.issn.1674-7445.2025150
Citation: Bai Le, Dai Ziqiang, Ren Zhipeng, et al. Dynamic analysis of immune responses in heterotopic heart transplantation model of genetically modified pig-to-macaque[J]. ORGAN TRANSPLANTATION. DOI: 10.12464/j.issn.1674-7445.2025150

Dynamic analysis of immune responses in heterotopic heart transplantation model of genetically modified pig-to-macaque

  • 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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