title: Tissue engineered bulking agent with adipose-derived stem cells and silk fibroin microspheres for the treatment of intrinsic urethral sphincter deficiency.
abstract: In this study we developed a tissue engineered bulking agent that consisted of adipose-derived stem cells (ADSCs) and silk fibroin microspheres to treat stress urinary incontinence caused by severe intrinsic sphincter deficiency (ISD). ISD models were established by completely transection of the bilateral pudendal nerve (PNT) and confirmed by the decreased leak-point pressure (LPP) and increased lumen area of urethra. Injection of silk fibroin microspheres could recover LPP and lumen area at 4 weeks but its efficacy disappears at 8, 12 weeks. Moreover, it was exciting to find that tissue engineered bulking agent brought long-term efficacy (at 4, 8, 12 weeks post-injection) on the recovery of LPP and lumen area. Concomitantly with the function, tissue engineered bulking agent treated group also improved the urethral sphincter structure as exhibited by better tissue regeneration. The findings showed that silk fibroin microspheres alone could work effectively in short-term, while tissue engineered bulking agent that combined silk fibroin microspheres with ADSCs exhibited promising long-term efficacy. This study developed a new strategy of tissue engineered bulking agent for future ISD therapy.
authors.affiliation: Department of Gynecology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China.
authors.forename: Li Bing
authors.initials: LB
authors.lastname: Shi
authors.affiliation: Department of Gynecology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China.
authors.forename: Hong Xia
authors.initials: HX
authors.lastname: Cai
authors.affiliation: Zhejiang Xinyue Biotechnology Co. Ltd., Hangzhou, Zhejiang 311121, PR China.
authors.forename: Long Kun
authors.initials: LK
authors.lastname: Chen
authors.affiliation: Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, Zhejiang 310058, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, Zhejiang 310058, PR China.
authors.forename: Shou An
authors.initials: SA
authors.lastname: Zhu
authors.affiliation: Center for Stem Cells and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China.
authors.forename: Xiao Nan
authors.initials: XN
authors.lastname: Gong
authors.affiliation: Department of Gynecology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China.
authors.forename: Ya Xian
authors.initials: YX
authors.lastname: Xia
authors.affiliation: Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, Zhejiang 310058, PR China; Center for Stem Cells and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China.
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Ouyang
authors.affiliation: Department of Gynecology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang 310003, PR China. Electronic address: zouxiaohui@zju.edu.cn.
authors.forename: Xiao Hui
authors.initials: XH
authors.lastname: Zou
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D005260:Female; D005349:Fibroins / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D051381:Rats; D017207:Rats, Sprague-Dawley; D047011:Silk / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering; D014521:Urethra / Q000503:physiopathology*; D014550:Urinary Incontinence, Stress / Q000503:physiopathology / Q000628:therapy*
chemical_list: D047011:Silk; D005349:Fibroins
keywords: Adipose-derived stem cells (ADSCs); Intrinsic sphincter deficiency (ISD); Periurethral injection; Pudendal nerve transection (PNT); Silk fibroin microspheres; Tissue engineered bulking agent