Pig regulatory macrophages (pMregs) represent the donor-derived immunoregulatory cells for xenotransplantation in the need of porcine graft resistance to the adaptive immune recognition with minimal inflammatory and coagulation-associated vascular injury. The key translational question is which parts of the pMreg profile can be considered reliable irrespective of the species identity of the donors, type of primates or humans as responders, responder burden pressure and macrophage-endothelial vascular readouts. RDCA, RTRA, JDEM, VCS, and LDFA structure the pMreg assay values into a transfer-reliability profile. CD14+ pig monocytes under M-CSF and IFN-γ conditioning yielded the cells analyzed by regulatory phenotype, cytokine production, CD4+ T-suppression in pigs and cynomolgus monkeys, Jurkat inhibition, FOXP3 up-regulation and human macrophage-pig endothelial transcript changes. CD14+ enrichment was elevated from 12.4% to 97.5%, DHRS9+ cell count was increased from 19.4% to 85.4%, IL-10 raised from 40 to 730 pg/mL, TGF-β was increased from 90 to 500 pg/mL, while IL-1β was decreased from 230 to 5 pg/mL. RDCA provided the balance-adjusted score of 0.623 suggesting the coordinated but non-equally balanced immune-vascular regulation. RTRA revealed that CD4+ suppression of cynomolgus monkeys and maximal inhibition of Jurkats preserved only 42.6% of the pMreg pig CD4+ reference effect, while FOXP3 induction of Jurkat kept 28.5% of the fold-change of pig FOXP3. JDEM demonstrated 74.6% loss of the 1:1 Jurkat inhibition effect due to the 1:5 pMreg:Jurkat ratio. VCS indicated the concordant transcript relief with cytokine-gene reduction of 60.2%, coagulation-associated reduction of 69.7% and concordance value of 0.926. LDFA found the major limiting readouts in the adaptive transfer and vascular quiescence rather than cell identity and regulatory secretion. Profile pMreg can thus be said to be most pronounced in terms of regulatory identity and vascular transcript agreement, but non-pig adaptive preservation, responder-burden longevity, and protein-level verification of TF/PAR-1 are the key pre-clinical considerations.