title: Urethral Reconstruction with Small Intestinal Submucosa Seeded with Oral Keratinocytes and TIMP-1 siRNA Transfected Fibroblasts in a Rabbit Model.
abstract: BACKGROUND
  To evaluate the effect of tissue inhibitor of metalloproteinase-1 small interfering RNA (TIMP-1 siRNA) transfected fibroblasts (FB) for urethral reconstruction.
  
  
  METHODS
  A ventral urethral mucosal defect was created. Substitution urethroplasty was performed with small intestinal submucosa (SIS) alone (8 rabbits, group 1), autogenic oral keratinocytes (OK)-seeded SIS (8 rabbits, group 2) or autogenic OK and TIMP-1 siRNA transfected FB-seeded SIS (8 rabbits, group 3). At 1 and 6 months after surgery (4 rabbits at each time point), retrograde urethrogram and histologic analysis were performed to evaluate the outcomes of urethroplasty.
  
  
  RESULTS
  TIMP-1 siRNA transfected FB decreased the secretion of type I collagen. Under retrograde urethrography, 5 rabbits in group 1, 6 in group 2 and 7 in group 3 maintained a wide urethral caliber. Histologically, inflammation and fibrosis were observed at 6 months in group 1. The speed of urothelium, smooth muscle and vessel regeneration in group 3 was faster than that in group 2. Comparison of smooth muscle-to-collagen ratio, epithelial layers, smooth muscle content and microvessel density among three groups revealed a significant increase (p < 0.05).
  
  
  CONCLUSIONS
  TIMP-1 siRNA transfected FB could be used as a source of seed cell for urethral tissue engineering and could prevent the proliferation of urethral scar tissue.
authors.affiliation: Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Guo
authors.forename: Yinglong
authors.initials: Y
authors.lastname: Sa
authors.forename: Jianwen
authors.initials: J
authors.lastname: Huang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Minkai
authors.initials: M
authors.lastname: Xie
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Lv
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D007413:Intestinal Mucosa / Q000378:metabolism / Q000637:transplantation*; D007421:Intestine, Small / Q000378:metabolism / Q000637:transplantation*; D015603:Keratinocytes / Q000378:metabolism / Q000637:transplantation*; D008297:Male; D009055:Mouth / Q000166:cytology; D034622:RNA Interference; D011817:Rabbits; D019651:Plastic Surgery Procedures; D012038:Regeneration; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014521:Urethra / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D014522:Urethral Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*
chemical_list: D024042:Collagen Type I; D019715:Tissue Inhibitor of Metalloproteinase-1