Comparative analysis of the immunomodulatory effects of extracellular vesicles from canine placental and adipose-derived mesenchymal stem cells.

PMSC-derived extracellular vesicles show strong immunosuppressive potential and may offer a novel acellular therapy for canine immune-mediated diseases.

This study compared the immunomodulatory properties of canine placenta-derived mesenchymal stem cells (PMSCs) and adipose-derived MSCs (ADMSCs), as well as their respective extracellular vesicles (EVs), on peripheral blood mononuclear cells (PBMCs). Both MSC types were isolated and characterized, then cocultured with PBMCs to assess viability, CD4 expression, proliferation, and inflammatory cytokine profiles (IL-2, IL-10, TNF-α). In direct MSC coculture experiments, PMSCs demonstrated superior immunosuppressive activity, evidenced by the lowest PBMC proliferation and viability, highest CD4 expression, and significantly reduced TNF-α levels compared to ADMSCs. IL-2 and IL-10 concentrations were similar between groups. In EV experiments, PMSC-derived EVs more effectively inhibited PBMC proliferation than ADMSC-derived EVs, and also produced the lowest PBMC viability and TNF-α concentrations. However, CD4 expression did not differ between EV groups, and IL-2 was lowest in the ADMSC EV group. These findings suggest that PMSCs and their EVs possess immunomodulatory capabilities comparable to, and in certain parameters superior to, ADMSCs. Given the acellular nature of EVs and their potential to avoid challenges associated with live-cell therapies, PMSC-derived EVs represent a promising therapeutic avenue for immune-mediated diseases in dogs. Further in vivo studies are warranted to validate these findings and evaluate clinical applicability.

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