Ureteral gene transfer to porcine induced strictures using endourologic delivery of an adenoviral vector.

Details

Serval ID
serval:BIB_E5B1C060DA76
Type
Article: article from journal or magazin.
Collection
Publications
Title
Ureteral gene transfer to porcine induced strictures using endourologic delivery of an adenoviral vector.
Journal
Journal of Urology
Author(s)
Anidjar M., Mongiat-Artus P., Brouland J.P., Cochand-Priollet B., Teillac P., Le Duc A., Berthon P., Cussenot O.
ISSN
0022-5347 (Print)
ISSN-L
0022-5347
Publication state
Published
Issued date
1999
Peer-reviewed
Oui
Volume
161
Number
5
Pages
1636-1643
Language
english
Abstract
PURPOSE: 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.
MATERIALS AND 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.
CONCLUSION: This data represents the first report of adenovirus-mediated gene transfer to the ureter. It remained site specific by endourologic retrograde clinically applicable techniques.
Keywords
Adenoviridae/genetics, Animals, Female, Gene Transfer Techniques, Genetic Therapy/methods, Swine, Ureter, Ureteral Obstruction/therapy, Ureteroscopy, beta-Galactosidase/genetics
Pubmed
Web of science
Create date
13/10/2015 9:24
Last modification date
20/08/2019 16:09
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