title: Transplantation of autologous differentiated urothelium in an experimental model of composite cystoplasty.
abstract: BACKGROUND
  Enterocystoplasty is associated with serious complications resulting from the chronic interaction between intestinal epithelium and urine. Composite cystoplasty is proposed as a means of overcoming these complications by substituting intestinal epithelium with tissue-engineered autologous urothelium.
  
  
  OBJECTIVE
  To develop a robust surgical procedure for composite cystoplasty and to determine if outcome is improved by transplantation of a differentiated urothelium.
  
  
  METHODS
  Bladder augmentation with in vitro-generated autologous tissues was performed in 11 female Large-White hybrid pigs in a well-equipped biomedical centre with operating facilities. Participants were a team comprising scientists, urologists, a veterinary surgeon, and a histopathologist.
  
  
  METHODS
  Urothelium harvested by open biopsy was expanded in culture and used to develop sheets of nondifferentiated or differentiated urothelium. The sheets were transplanted onto a vascularised, de-epithelialised, seromuscular colonic segment at the time of bladder augmentation. After removal of catheters and balloon at two weeks, voiding behaviour was monitored and animals were sacrificed at 3 months for immunohistology.
  
  
  CONCLUSIONS
  Eleven pigs underwent augmentation, but four were lost to complications. Voiding behaviour was normal in the remainder. At autopsy, reconstructed bladders were healthy, lined by confluent urothelium, and showed no fibrosis, mucus, calculi, or colonic regrowth. Urothelial morphology was transitional with variable columnar attributes consistent between native and augmented segments. Bladders reconstructed with differentiated cell sheets had fewer lymphocytes infiltrating the lamina propria, indicating more effective urinary barrier function.
  
  
  CONCLUSIONS
  The study endorses the potential for composite cystoplasty by (1) successfully developing reliable techniques for transplanting urothelium onto a prepared, vascularised, smooth muscle segment and (2) creating a functional urothelium-lined augmentation to overcome the complications of conventional enterocystoplasty.
authors.affiliation: Jack Birch Unit for Molecular Carcinogenesis, Department of Biology, University of York, York, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Turner
authors.forename: Ramnath
authors.initials: R
authors.lastname: Subramanian
authors.forename: David F M
authors.initials: DF
authors.lastname: Thomas
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hinley
authors.forename: Syed Khawar
authors.initials: SK
authors.lastname: Abbas
authors.forename: Jens
authors.initials: J
authors.lastname: Stahlschmidt
authors.forename: Jennifer
authors.initials: J
authors.lastname: Southgate
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology; D005260:Female; D016130:Immunophenotyping; D023421:Models, Animal; D011183:Postoperative Complications; D019651:Plastic Surgery Procedures / Q000379:methods*; D034421:Sus scrofa; D023822:Tissue Engineering / Q000379:methods*; D020858:Tissue and Organ Harvesting / Q000379:methods; D014182:Transplantation, Autologous; D001743:Urinary Bladder / Q000601:surgery*; D019459:Urothelium / Q000166:cytology / Q000637:transplantation*