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

Area of Science:

• Regenerative Medicine
• Cell Therapy
• Urology

Background:

• Stress urinary incontinence (SUI) is linked to pelvic floor damage and impaired extracellular matrix (ECM) remodeling.
• Fibroblast dysfunction is a key factor in SUI pathogenesis.
• Current treatments for SUI have limitations, necessitating novel therapeutic strategies.

Purpose of the Study:

• To investigate the regenerative capacity of decidua-derived mesenchymal stromal cells (DMSCs) for SUI.
• To elucidate the molecular mechanisms by which DMSCs promote tissue repair in SUI.
• To evaluate DMSC efficacy in both an in vivo rat model and an in vitro human cell model.

Main Methods:

• Adult female rats underwent vaginal distension (VD) to model SUI and received periurethral DMSC injections.
• Functional (leak point pressure) and transcriptomic analyses were performed at one and six weeks post-VD.
• An in vitro co-culture system assessed the paracrine effects of DMSCs on human SUI fibroblasts.

Main Results:

• DMSC treatment significantly improved leak point pressure in rats, indicating enhanced urethral function.
• Transcriptomic analysis revealed DMSC-induced changes consistent with tissue repair, including modulated proliferation and inflammation markers.
• In vitro, DMSCs reduced senescence markers (p16) and rebalanced ECM remodeling by altering matrix metalloproteinase (MMP) activity.

Conclusions:

• DMSCs promote a regenerative microenvironment by modulating cellular senescence and ECM dynamics.
• DMSCs enhance tissue repair and functional recovery in preclinical models of SUI.
• DMSCs represent a promising disease-modifying cell therapy for stress urinary incontinence.