Human umbilical cord mesenchymal stromal cells and their small extracellular vesicles modulate host responses to titanium-coated polypropylene mesh in the vaginal wall of rats

Objective To assess whether human umbilical cord mesenchymal stromal cells (HUCMSCs) or HUCMSC-derived small extracellular vesicles (HUCMSC-sEVs) modify tissue responses to titanium-coated polypropylene mesh in the rat vaginal wall. Methods Fifty-four ovariectomized female Sprague–Dawley rats were randomly assigned to saline-control, HUCMSC-sEV, or HUCMSC groups (18 each). After mesh implantation, animals received one 0.3-mL local injection. Independent cohorts were assessed at 1, 4, and 12 weeks. Hematoxylin and eosin staining evaluated inflammatory cell infiltration, neovascularization, and fibrous encapsulation; picrosirius red staining assessed collagen composition and the COL I/COL III ratio; and quantitative real-time polymerase chain reaction measured inflammation- and matrix-remodeling-related genes. The animal was the experimental unit, and false discovery rate adjustment was applied to multiple comparisons. Results At week 1, inflammatory cell infiltration was lower in the HUCMSC-sEV group than in the saline-control group, while interleukin-10, interleukin-12, and tumor necrosis factor-α mRNA expression was lower in both intervention groups. At week 4, both interventions reduced fibrous encapsulation and increased matrix metalloproteinase-2 and -9 mRNA expression. At week 12, the type I/type III collagen ratio was lower in both intervention groups, matrix metalloproteinase-2 and -9 mRNA expression was higher in both intervention groups, and type III collagen gene expression was higher in the HUCMSC group. Conclusion HUCMSCs and HUCMSC-sEVs were associated with changes in early inflammatory cell infiltration and cytokine-transcript expression, fibrous encapsulation, and later collagen- and matrix-related measures after mesh implantation. The partially overlapping response patterns observed between HUCMSC-sEVs and HUCMSCs support further investigation of HUCMSC-sEVs as a cell-free approach to modulating mesh-associated host responses.