A Cell-Based Therapeutic Strategy for Stress Urinary Incontinence: Functional and Molecular Evidence from...

Stress urinary incontinence (SUI) is a highly prevalent condition associated with pelvic floor damage, fibroblast dysfunction, and impaired extracellular matrix (ECM) remodeling. This study aimed to investigate the regenerative potential and underlying molecular mechanisms of decidua-derived mesenchymal stromal cells (DMSCs) in a rat model of vaginal distension (VD) and in human suburethral fibroblasts from SUI patients. Adult female rats were subjected to VD and treated with periurethral DMSC injections, followed by functional and transcriptomic analyses, one and six weeks after VD. In parallel, an in vitro co-culture system was used to evaluate the paracrine effects of DMSCs on SUI fibroblasts. DMSC treatment significantly increased leak point pressure (LPP) one week after VD, approaching values observed in control animals (19.8 ± 0.45 vs. 22.3 ± 2.08 mmHg, p = 0.09), while promoting transcriptional changes consistent with tissue repair. Gene expression analyses revealed transient increases in proliferative and inflammatory markers, followed by earlier normalization compared to untreated animals. In vitro, DMSCs reduced p16 expression, increased p21 and Klotho levels, and rebalanced ECM remodeling by decreasing MMP-1 and increasing MMP-2. These findings indicate that DMSCs promote a regenerative microenvironment by modulating senescence and ECM dynamics. Overall, DMSCs may represent a promising disease-modifying strategy for SUI by enhancing tissue repair and functional recovery.