eMSC EXOs immunomodulatory effects on macrophages. (A) Both Crude and CD146+ eMSC EXOs were internalized in PMA/IO-stimulated THP-1 (blue, nucleus; red, EXOs). (B) PMA/IO-stimulated THP-1 molecular profiling indicated a strong shift in genes towards M2 macrophage polarization by both Crude and CD146+ eMSC EXOs. The dotted line represents the stimulated THP-1 gene levels without exposure to eMSC EXOs. (C) The in silico prediction scoring system revealed MRC1 as a target for hsa-miR-1255a and hsa-miR-3065-5p (60% and 71% probability, respectively), TGFB1 as a target for hsa-let-7e-5p (59%), and CCL2 as a target for hsa-miR-125a (51%). All four miRNAs were highly present in both Crude and CD146+ eMSC EXOs. (D) eMSC EXOs significantly increased secretion of M2-polarization-related molecules in PMA/IO-stimulated THP-1 compared to stimulated THP-1 alone (*, p < 0.05). (E) Crude and CD146+ eMSC EXOs exposure of PMA/IO-stimulated THP-1 resulted in reduced capacity to phagocytize fluorescent bioparticles (19 ± 4% and 24 ± 2%, respectively).