title: Terminal urothelium differentiation of engineered neoureter after in vivo maturation in the "omental bioreactor".
abstract: OBJECTIVE
  Long ureteric defects may theoretically be repaired with the use of tissue-engineered neoureter. However, attempts to construct such a neoureter in animal models have failed because of major inflammatory response. Avoidance of such inflammation requires a well-differentiated urothelium. We investigated whether omental maturation of a seeded construct in a pig model could achieve terminal differentiation of the urothelium to allow construction of a stricture-free neoureter.
  
  
  METHODS
  Bladder biopsies were taken to allow urothelial and smooth muscle cell cultures. These cultured cells were used to seed small intestinal submucosa (SIS) matrix. After 2 wk of cell growth, the in vitro SIS-seeded construct was shaped around a silicone drain and wrapped by the omentum to obtain neoureters. These neoureters were left in the omentum without any contact with urine, and then harvested 3 wk later for histologic and immunohistochemical studies.
  
  
  RESULTS
  Before implantation, the in vitro constructs were composed of a mono- or bilayer of undifferentiated urothelium overlying a monolayer of smooth muscle cells. After 3 wk of omental maturation, these constructs were vascularized and comprised a terminally differentiated multilayered urothelium with umbrella cells over connective tissue and smooth muscle cells, with no evidence of fibrosis or inflammation.
  
  
  CONCLUSIONS
  We obtained, for the first time, with this model of in vivo maturation in the omentum, a mature neoureter composed of a well-differentiated multilayered urothelium.
authors.affiliation: Department of Urology, Paris Saint Joseph Hospital Trust, Paris, France. baumertherve@yahoo.fr
authors.forename: Hervé
authors.initials: H
authors.lastname: Baumert
authors.forename: Dhouha
authors.initials: D
authors.lastname: Mansouri
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Fromont
authors.forename: Mehrak
authors.initials: M
authors.lastname: Hekmati
authors.forename: Pascal
authors.initials: P
authors.lastname: Simon
authors.forename: Walid
authors.initials: W
authors.lastname: Massoud
authors.forename: Vincent
authors.initials: V
authors.lastname: Molinié
authors.forename: Bernard
authors.initials: B
authors.lastname: Malavaud
mesh_terms: D000818:Animals; D019149:Bioreactors; D002454:Cell Differentiation; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D009130:Muscle, Smooth / Q000166:cytology / Q000637:transplantation; D009852:Omentum; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014517:Ureteral Obstruction / Q000601:surgery*; D019459:Urothelium / Q000166:cytology / Q000637:transplantation*