4 years ago

Controlled release of IGF1 enhances urethral sphincter function and histological structure in the treatment of female stress urinary incontinence in a rodent model

Anthony Atala, Yuanyuan Zhang, Shicheng Wei, Jian Yang, Margot Damaser, Hao Yan, Emmanuel Opara, Yaodong Jiang, Liren Zhong, Xiangming Mao, Junhong Deng
Objectives Stress urinary incontinence (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. The goal of this study was to determine the effects of controlled release of IGF1 from alginate-poly-L-ornithine-gelatin microbeads (IGF1-A-PLO-G microbeads) on sphincter tissue regeneration in a rat model of SUI. Materials and Methods Forty-four female SD rats were randomized into 4 groups: vaginal distension followed by periurethral injection of IGF1-A-PLO-G beads (VD+IGF1 microbeads): 1x104 beads/1 ml normal saline; VD+empty microbeads; VD+saline; or sham VD+saline (sham). Results Urethral function (leak point pressure, LPP) was significantly decreased 1 week after VD+saline (23.9 ± 1.3 cmH2O) or VD+empty microbeads (21.7 ± 0.8 cmH2O) compared to the sham group (44.4 ± 3.4 cmH2O; p<0.05), demonstrating that the microbeads themselves do not create a bulking or obstructive effect in the urethra. LPP significantly increased 1 week after VD+IGF1 microbeads (28.4 ± 1.2 cmH2O), compared to VD+empty microbeads (p<0.05) and was not significantly different from LPP in sham rats, demonstrating initiation of a reparative effect even 1 week after VD. Histological analysis demonstrated well-organized skeletal muscle fibers and vascular development in the external urethral sphincter 1 week after VD+IGF1 microbeads, compared to the substantial muscle fiber attenuation and disorganization, and less vascular formation 1 week after VD+saline or VD+empty microbeads. Conclusion Periurethral administration of IGF1-A-PLO-G beads facilitates recovery from SUI by promoting skeletal myogenesis and revascularization. This therapy is promising, but detailed and longer term studies in animal models and humans should be done. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/bju.13985

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