Adipose-derived stem cell exosomes for stress urinary incontinence: a novel in vivo therapeutic approach

This study aimed to evaluate the therapeutic effects of adipose tissue-derived stem cell exosomes (ADSCE) in the management of stress urinary incontinence (SUI) using vaginal dilatation-induced acute and chronic SUI models in Sprague-Dawley rats. The model for acute and chronic SUI was established via single and repeated vaginal dilatation, respectively. Mesenchymal cells, mesenchymal stem cells, and exosomes were isolated. Flow cytometry confirmed the mesenchymal identity of isolated stem cells, while exosomal markers (CD9, CD63, CD81) validated successful exosome isolation. Transmission electron microscopy revealed the characteristic nanoscale morphology of exosomes, further supported by energy-dispersive X-ray analysis. Rats were treated with the exosomes locally and vaginally. Therapeutic efficacy was assessed through urodynamic and histopathological analyses. Abdominal leak point pressure (ALPP) was significantly reduced in both acute and chronic SUI models compared to controls (P < 0.0001). ADSCE therapy significantly increased ALPP, with systemic administration demonstrating superior efficacy over local treatment (P < 0.05). Histopathological examination indicated substantial sphincter muscle thinning, edema, and fibrosis in untreated models, while exosome therapy mitigated these pathological changes. Masson's Trichrome staining revealed significant preservation of urethral sphincter thickness in treated groups (P < 0.01), with systemic therapy yielding moderate improvements over local administration. Furthermore, exosome therapy markedly reduced collagen deposition, particularly in systemic treatment groups, suggesting an antifibrotic effect and enhanced tissue remodeling. These findings indicate that ADSCE effectively restores urethral function and mitigates pathological alterations in SUI. Systemic administration demonstrates superior therapeutic potential, highlighting ADSCE therapy as a promising regenerative strategy for SUI management.