Controlled release of insulin-like growth factor 1 enhances urethral sphincter function and histological structure in the treatment of female stress urinary incontinence in a rat model

Abstract

Objectives: To determine the effects of controlled release of insulin-like growth factor 1 (IGF-1) from alginate-poly-L-ornithine-gelatine (A-PLO-G) microbeads on external urethral sphincter (EUS) tissue regeneration in a rat model of stress urinary incontinence (SUI), as SUI diminishes the quality of life of millions, particularly women who have delivered vaginally, which can injure the urethral sphincter. Despite several well-established treatments for SUI, growth factor therapy might provide an alternative to promote urethral sphincter repair. Materials and Methods: In all, 44 female Sprague-Dawley rats were randomised into four groups: vaginal distension (VD) followed by periurethral injection of IGF-1-A-PLO-G microbeads (VD + IGF-1 microbeads; 1 × 104 microbeads/1 mL normal saline); VD + empty microbeads; VD + saline; or sham-VD + saline (sham). Results: Urethral function (leak-point pressure, LPP) was significantly lesser 1 week after VD + saline [mean (sem) 23.9 (1.3) cmH2O] or VD + empty microbeads [mean (sem) 21.7 (0.8) cmH2O) compared to the sham group [mean (sem) 44.4 (3.4) cmH2O; P < 0.05), indicating that the microbeads themselves do not create a bulking or obstructive effect in the urethra. The LPP was significantly higher 1 week after VD + IGF-1 microbeads [mean (sem) 28.4 (1.2) cmH2O] compared to VD + empty microbeads (P < 0.05), and was not significantly different from the LPP in sham rats, demonstrating an initiation of a reparative effect even at 1 week after VD. Histological analysis showed well-organised skeletal muscle fibres and vascular development in the EUS at 1 week after VD + IGF-1 microbeads, compared to substantial muscle fibre attenuation and disorganisation, and less vascular formation at 1 week after VD + saline or VD + empty microbeads. Conclusion: Periurethral administration of IGF-1-A-PLO-G microbeads facilitates recovery from SUI by promoting skeletal myogenesis and revascularisation. This therapy is promising, but detailed and longer term studies in animal models and humans are needed.