title: Ureteral gene transfer to porcine induced strictures using endourologic delivery of an adenoviral vector.
abstract: OBJECTIVE
  Direct gene transfer to the ureter is an attractive approach to prevent restenosis after endourologic management of ureteral strictures. We therefore assessed the rationale for adenovirus-mediated gene transfer in the ureter in vitro and in vivo using a porcine model.
  
  
  METHODS
  Primary cultures of porcine ureteral epithelial and stromal cells were infected with an adenoviral solution carrying a nucleus-targeted beta-Galactosidase (beta-Gal) reporter gene (6.5 10(8) pfu/ml.). In addition, in order to mimic the human clinical situation, we have devised a model of thermally-induced stricture in porcine ureter which produced tight fibrotic stenosis within 8 days. Using a purposely designed channelled balloon catheter prototype, these strictures were endoscopically dilated and then instilled with the same beta-Gal adenoviral construction.
  
  
  RESULTS
  Application of recombinant adenovirus harboring a nucleus-targeted beta-Gal reporter gene to cultured porcine urothelial and stromal cells resulted in high transduction efficiency of up to 99% and 84% respectively. Seven days after infection, X-Gal staining of the strictured ureters demonstrated transfection up to 2 mm. depth within the fibrosis, confirmed by polymerase chain reaction (PCR) analysis. Adjacent and distal spread of the virus was excluded by histochemistry (X-Gal staining) and PCR.
  
  
  CONCLUSIONS
  This data represents the first report of adenovirus-mediated gene transfer to the ureter. It remained site specific by endourologic retrograde clinically applicable techniques.
authors: Département d'Urologie, Hôpital Saint-Louis, Paris, France.
authors: M
authors: M
authors: Anidjar
authors: P
authors: P
authors: Mongiat-Artus
authors: J P
authors: JP
authors: Brouland
authors: B
authors: B
authors: Cochand-Priollet
authors: P
authors: P
authors: Teillac
authors: A
authors: A
authors: Le Duc
authors: P
authors: P
authors: Berthon
authors: O
authors: O
authors: Cussenot
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D013552:Swine; D014513:Ureter; D014517:Ureteral Obstruction / Q000628:therapy*; D018666:Ureteroscopy; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D001616:beta-Galactosidase