W208 - Immunosuppressive Potential of hUC-MSCs: Modulating Macrophage-Driven Inflammation Through Direct and Paracrine Mechanisms

Abstract Text: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are emerging as potent immunomodulators with significant therapeutic potential in inflammatory and immune-mediated diseases. Macrophages, particularly the pro-inflammatory M1 phenotype, play a pivotal role in mediating pathological inflammation by producing nitric oxide (NO) and inflammatory cytokines. This study investigates the effects of human umbilical cord-derived MSCs (hUC-MSCs) on inflammation and nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. The Griess assay demonstrated that LPS stimulation significantly increased NO production, whereas co-culture with hUC-MSCs led to a time- and dose-dependent reduction in NO levels. The highest MSC ratio (1:2) resulted in a significant decrease in NO, with conditioned media (CM) showing a greater NO-suppressive effect than direct co-culture. Cytokine analysis revealed the dynamic immunomodulatory effects of hUC-MSCs. While MSC co-culture initially suppressed TNF levels at 12 hours, this effect was not sustained, with TNF increasing at later time points. IL-6 levels were significantly elevated at 12 hours but showed a delayed suppressive effect at 24 hours. MCP-1 was consistently reduced across all co-culture conditions, indicating prolonged suppression. IL-10 secretion was significantly increased at 12 hours, with sustained elevation at 24 and 48 hours, particularly in direct co-culture groups. However, IL-12p70 and IFN-γ levels remained largely unaffected. These findings highlight the potential of hUC-MSCs to modulate inflammation through NO inhibition and cytokine regulation, suggesting their therapeutic utility in inflammatory lung conditions.