title: Activation of VEGF and ERK1/2 and improvement of urethral function by adipose-derived stem cells in a rat stress urinary incontinence model.
abstract: OBJECTIVE
  To investigate the injected autologous adipose-derived stem cells (ADSCs) in improving stress urinary incontinence in a rodent model of parturition-related stress incontinence and the possible mechanism.
  
  
  METHODS
  The 40 rats were developed stress urinary incontinence models by postpartum balloon dilation of the vagina for 4 hours followed by bilateral ovariectomy. ADSCs were isolated from the peri-ovarian fat and labeled with thymidine analog 5-ethynyl-2-deoxyuridine (EdU). Twenty stress urinary incontinence rats received peri-urethral injection of phosphate-buffered saline as the negative controls and the other 20 stress urinary incontinence rats received peri-urethral injection of EdU-labeled ADSCc. Twenty control rats underwent sham ovariectomy without balloon dilation and served as positive controls. Four weeks later, voiding function was assessed by cystometry. Urethral histologic examination (Masson trichrome stain, picrosirius red stain, Hart elastin stain, Gordon and Sweet stain, and immunohistochemical stain) and Western blot were performed on urethral tissues.
  
  
  RESULTS
  Both leak point pressure and bladder capacity were significantly increased in ADSC-treated rats, compared to the balloon-injured ovariectomized rats. Histologic examination revealed normalized appearance of the fibromuscular structure of the urethra as well as increased peri-urethral blood vessel density in ADSC-treated rats. On Western blot, vascular endothelial growth factor and P-extracellular signal-regulated kinases (ERKs)1/2 protein was expressed at a higher rate in tissues from ADSC-treated rats compared to phosphate-buffered saline-treated rats.
  
  
  CONCLUSIONS
  Peri-urethral injection of ADSCs is associated with more normal urinary function and urethral structure in rats with parturition-related incontinence. The activation of vascular endothelial growth factor and ERK1/2 may be responsible for the paracrine effects from ADSCs.
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, China.
authors.forename: Guang-Yong
authors.initials: GY
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Gong
authors.forename: Wan-Shou
authors.initials: WS
authors.lastname: Cui
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Yuan
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Song
authors.forename: Hua
authors.initials: H
authors.lastname: Xin
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Wei-Ren
authors.initials: WR
authors.lastname: Li
authors.forename: Zhe-Zhu
authors.initials: ZZ
authors.lastname: Gao
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Ying-Lu
authors.initials: YL
authors.lastname: Guo
authors.forename: Zhong-Cheng
authors.initials: ZC
authors.lastname: Xin
mesh_terms: D000273:Adipose Tissue / Q000637:transplantation*; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D020935:MAP Kinase Signaling System; D009130:Muscle, Smooth / Q000473:pathology; D054792:Muscle, Striated / Q000473:pathology; D018919:Neovascularization, Physiologic; D010052:Ovariectomy; D036801:Parturition; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D014521:Urethra / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001743:Urinary Bladder / Q000502:physiology; D014550:Urinary Incontinence, Stress / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D014554:Urination / Q000502:physiology; D014563:Urodynamics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D042461:Vascular Endothelial Growth Factor A