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
机构：[1]Biomedical Engineering Department of the Lerner Research Institute, Cleveland, OH, USA,[2]Department of Urology, Xuanwu Hospital, Capital Medical University, Beijing, China,泌尿外科首都医科大学宣武医院[3]Institute for Regenerative Medicine, Wake Forest University, Winston-Salem, NC, USA,[4]Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China,[5]Department of Andrology, The First People’s Hospital of Guangzhou, Guangzhou, Guangdong, China,[6]Laboratory of Biomaterials and Regenerative Medicine, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China,[7]Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, China,[8]The Advanced Platform Technology Center of the Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA,[9]Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA
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 x 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) cmH(2)O] or VD + empty microbeads [mean (SEM) 21.7 (0.8) cmH(2)O) compared to the sham group [mean (SEM) 44.4 (3.4) cmH(2)O; 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) cmH(2)O] 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.
基金：
R56 DK100669-01A1 support
the Cleveland Clinic and the Rehabilitation R&D Service of the Department of Veterans Affairs
第一作者机构：[1]Biomedical Engineering Department of the Lerner Research Institute, Cleveland, OH, USA,[2]Department of Urology, Xuanwu Hospital, Capital Medical University, Beijing, China,
通讯作者：
通讯机构：[*1]Wake Forest Institute For Regenerative Medicine, 391 Technology way, Winston-Salem, NA 27101, USA.[*2]Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
推荐引用方式(GB/T 7714)：
Hao Yan,Liren Zhong,Yaodong Jiang,et al.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[J].BJU INTERNATIONAL.2018,121(2):301-312.doi:10.1111/bju.13985.
APA：
Hao Yan,Liren Zhong,Yaodong Jiang,Jian Yang,Junhong Deng...&Yuanyuan Zhang.(2018).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.BJU INTERNATIONAL,121,(2)
MLA：
Hao Yan,et al."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".BJU INTERNATIONAL 121..2(2018):301-312
