Synergistic effects of urine-derived stem cells and platelet lysate on urethral sphincter regeneration in a rat model of pudendal nerve injury

Abstract Background Stress urinary incontinence (SUI) results from urethral sphincter insufficiency. Urine-derived stem cells (USCs) possess myogenic and neurotrophic potential, while platelet lysate (PL), enriched with PDGF, VEGF, TGF-β1, and EGF, enhances stem cell proliferation and engraftment. This study comprehensively evaluated the therapeutic efficacy of USCs alone, PL alone, and their combination in a pudendal nerve injury (PNI)-induced rat model of SUI. Methods Thirty female Sprague–Dawley rats were assigned to five groups (n = 6): Ctrl, PNI, PNI+Cell, PNI + PL, and PNI+Cell + PL. One week after surgical PNI induction, 1 × 10⁵ USCs in PBS, PBS with 10% PL, or USCs in PBS with 10% PL were injected into the external urethral sphincter. Conscious urodynamic studies assessed leak point pressure (LPP) and closing pressure (CP) at days 3, 7, and 14. Urethral sphincteric tissues were analyzed by H&E, Masson's trichrome, immunohistochemistry (nAChRα1, α-SMA, neurofilament), and quantitative PCR for myogenic (Pax7, MyoD, Myogenin, Mef2) and neuronal markers (GFAP, β-tubulin III, Neurofilament, MAP2). Results PNI significantly reduced LPP and CP. The PNI+Cell + PL group demonstrated the greatest functional recovery, with LPP approaching control levels at day 14. Combined treatment most effectively upregulated myogenic and neuronal markers, normalized MyoD expression, preserved muscle architecture, reduced fibrosis, and restored nAChRα1, α-SMA, and neurofilament expression compared with either monotherapy. Conclusions USC and PL combination therapy synergistically restored urethral sphincter function and promoted neuromuscular regeneration superior to either treatment alone, representing a promising regenerative strategy for SUI.