The temporal course of adenovirus-mediated gene transfer in the rat larynx.
OBJECTIVE
Polypeptide growth factors have important influences on wound-healing and scar tissue formation. Specific growth factors or their inhibitors may potentially decrease scar tissue formation and prevent subglottic stenosis. Gene transfer using recombinant adenovirus may be an ideal method to mediate endogenous production of growth factors to inhibit fibrosis.


METHODS
The study incorporated adenovirus-mediated transduction of normal and stenotic rat larynges and histologic analysis of the sequential expression of a beta-galactosidase marker gene over time.


METHODS
The study was conducted at the animal care facility of an academic children's hospital.


RESULTS
We report successful transduction in normal and injured rat larynx with peak expression of beta-galactosidase at 2 days after transduction and almost complete disappearance by 7 days. There appeared to be an early inflammatory response to the viral injection, but at 7 and 14 days after injection (transduction) the uninjured rat larynges resumed a normal histologic appearance. All distant sites stained negative for beta-galactosidase.


CONCLUSIONS
Recombinant adenovirus-mediated gene transfer is feasible in the rat larynx with transient duration and limited toxicity.


CONCLUSIONS
Adenovirus-mediated gene transfer has the potential to deliver growth factors that modulate wound healing and inflammation in the larynx by inhibiting fibrosis.
Jacobs
Ian N
IN
Division of Pediatric Otolaryngology, Children's Institute for Surgical Science, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 19104, USA. jacobsi@email.chop.edu
Tufano
Ralph P
RP
Walsh
Danielle S
DS
Crombleholme
Timothy
T
D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D000818:Animals; D005240:Feasibility Studies; D005355:Fibrosis; D017930:Genes, Reporter; D006133:Growth Substances / Q000096:biosynthesis; D007111:Immunity, Cellular; D007827:Laryngitis / Q000473:pathology; D007829:Laryngostenosis / Q000201:enzymology / Q000628:therapy*; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic / Q000379:methods; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics*
D006133:Growth Substances; D001616:beta-Galactosidase