title: Introducing a large animal model to create urethral stricture similar to human stricture disease: a comparative experimental microscopic study.
abstract: OBJECTIVE
  In this tissue engineering study we investigated urethral stricture formation to evaluate different treatment modalities in the large animal model and validate the most current, comparable effect of human stricture development for successful human clinical application.
  
  
  METHODS
  In 12 male minipigs stricture formation was evaluated by urethrography 1, 8 and 12 weeks after stricture induction by ligation, urethrotomy or thermocoagulation. Normal human urethral and scar tissue of 6 patients was harvested and compared to animal specimens. The effect of urethral damage was investigated for microvessel density and collagen I:III ratio.
  
  
  RESULTS
  A week after urethrotomy urothelium covered the spongiosum tissue, showing minimal infiltration of lymphocytes and macrophages, and sporadic eosinophil granulocytes. However, increased connective tissue was observed with time as well as urethral luminal narrowing, vascular network loss (decreased microvessel density) and significantly increased collagen with a favorably revised collagen type I:III ratio. The 3 methods of stricture induction resulted in different stricture severity in the animal model (thermocoagulation >ligation >urethrotomy). Porcine urethral samples after thermocoagulation showed a significantly increased collagen I:III ratio (p <0.001), almost equal to that of human urethral stricture specimens.
  
  
  CONCLUSIONS
  We successfully developed a large animal model in which to study urethral stricture formation by defined iatrogenic intervention. The established animal model advances investigation to evaluate new therapy modalities in a preclinical setting to treat urethral stricture and predict clinical outcome.
authors.affiliation: Department of Urology, THG-Surgery/Experimental Medicine (TOG), Eberhard-Karls-University, Tübingen, Germany. karl.sievert@med.uni-tuebingen.de
authors.forename: Karl-Dietrich
authors.initials: KD
authors.lastname: Sievert
authors.forename: Christian
authors.initials: C
authors.lastname: Selent-Stier
authors.forename: J
authors.initials: J
authors.lastname: Wiedemann
authors.forename: T-O
authors.initials: TO
authors.lastname: Greiner
authors.forename: Bastian
authors.initials: B
authors.lastname: Amend
authors.forename: A
authors.initials: A
authors.lastname: Stenzl
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Feil
authors.forename: J
authors.initials: J
authors.lastname: Seibold
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D006801:Humans; D007049:Iatrogenic Disease; D007150:Immunohistochemistry; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D013552:Swine; D013556:Swine, Miniature; D023822:Tissue Engineering; D014525:Urethral Stricture / Q000209:etiology / Q000473:pathology / Q000628:therapy*