Mesenchymal Stromal Cell-Derived Extracellular Vesicles for Oral Mucosal Engraftment in Urethral Reconstruction: Influence of Tissue Origin and Culture Growth Phase (Log vs. Stationary) on miRNA Content

Urethral stricture involves fibrotic narrowing of the urethral mucosa and spongiosum. Although urethroplasty using oral mucosal grafts is the gold standard for complex cases due to its high success rate, technical complexity limits its broader adoption. To address this, endoscopic transplantation of oral mucosal tissue has been proposed. While feasibility has been demonstrated, clinical efficacy remains suboptimal. Developing adjunctive factors that facilitate mucosal engraftment may improve outcomes of endoscopic transplantation. Extracellular vesicles (EVs)-membrane-bound nanoparticles secreted by cells that deliver miRNAs and other bioactive molecules-have recently emerged as promising candidates. We investigated EVs derived from four mesenchymal stromal cell (MSC) sources-stem cells from human exfoliated deciduous teeth (SHED), adipose tissue, umbilical cord, and bone marrow (BM)-isolated during both logarithmic (log) and stationary culture phases. miRNA profiling revealed distinct phase- and origin-specific signatures. SHED-derived EVs from the log phase and bone marrow-derived EVs from the stationary phase expressed miR-31, the let-7 family, and miR-205, suggesting early wound healing potential. In contrast, stationary-phase SHED-EVs and log-phase BM-MSC-EVs were enriched in the miR-99 family and miR-31, indicating potential roles in epithelial stabilization and fibrosis modulation. These findings support phase-specific application of MSC-EVs to optimize mucosal engraftment in transurethral reconstruction.