Hao Yan1,2, Liren Zhong3,4, Yaodong Jiang3,4, Jian Yang3, Junhong Deng5, Shicheng Wei6, Emmanuel Opara4, Anthony Atala3, Xiangming Mao7, Margot S Damaser1,8,9, Yuanyuan Zhang3. 1. Biomedical Engineering Department of the Lerner Research Institute, Cleveland, OH, USA. 2. Department of Urology, Xuanwu Hospital, Capital Medical University, Beijing, China. 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.
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) cmH2 O] or VD + empty microbeads [mean (sem) 21.7 (0.8) cmH2 O) compared to the sham group [mean (sem) 44.4 (3.4) cmH2 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) cmH2 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.
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) cmH2 O] or VD + empty microbeads [mean (sem) 21.7 (0.8) cmH2 O) compared to the sham group [mean (sem) 44.4 (3.4) cmH2 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) cmH2 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.
Authors: J P McQuilling; J Arenas-Herrera; C Childers; R A Pareta; O Khanna; B Jiang; E M Brey; A C Farney; E C Opara Journal: Transplant Proc Date: 2011-11 Impact factor: 1.066
Authors: Hui Q Pan; James M Kerns; Dan L Lin; David Sypert; James Steward; Christopher R V Hoover; Paul Zaszczurynski; Robert S Butler; Margot S Damaser Journal: Am J Physiol Renal Physiol Date: 2008-12-17
Authors: Zahra Rashidbenam; Mohd Hafidzul Jasman; Pezhman Hafez; Guan Hee Tan; Eng Hong Goh; Xeng Inn Fam; Christopher Chee Kong Ho; Zulkifli Md Zainuddin; Reynu Rajan; Fatimah Mohd Nor; Mohamad Aznan Shuhaili; Nik Ritza Kosai; Farrah Hani Imran; Min Hwei Ng Journal: Tissue Eng Regen Med Date: 2019-05-22 Impact factor: 4.169