A first-in-human pilot study of Wharton’s jelly-derived mesenchymal stem cell injection for urethral stricture: safety and preliminary efficacy

Urethral stricture is a fibrotic narrowing of the urethra with limited long-term success using minimally invasive treatments. Mesenchymal stem cells (MSCs) possess antifibrotic and regenerative properties that may offer a novel therapeutic approach. This first-in-human pilot study evaluated the safety and preliminary efficacy of Wharton’s jelly-derived MSC injections for recurrent bulbar urethral stricture. Eleven men with recurrent bulbar urethral strictures ≤ 2 cm underwent urethral dilatation followed 3–5 days later by intralesional injection of 4 × 10^6 MSCs. MSCs were cryopreserved under ultra-low temperatures, transported at 2–8 °C on the day of injection, and viability (> 70%) was confirmed post-thaw. Patients were followed for six months, with assessments including uroflowmetry, post-void residual, urethroscopy or retrograde urethrography, and patient-reported outcomes (IPSS, IIEF, USS-PROM). Safety was monitored throughout. The procedure was completed in all patients without technical difficulties. No systemic or long-term local adverse events were observed. Two patients experienced transient dysuria and one had minimal hematuria, all resolving spontaneously. Median Qmax improved from 8.9 mL/s preoperatively to 16.4 mL/s at 1 month but declined toward baseline by 6 months. Patient-reported outcomes showed short-term improvements, with significant reductions in IPSS and USS-PROM scores at 1 and 3 months. No statistically significant changes were observed in uroflowmetry parameters over the six-month follow-up. Intralesional injection of Wharton’s jelly-derived MSCs following urethral dilatation is safe and feasible in humans. While objective urinary flow improvements were limited, patient-reported symptoms showed short-term benefit. These findings support further investigation in larger, controlled trials to optimize dosing, evaluate repeated administration, and determine efficacy in urethral stricture management.