The use of newborn rats and an adenoviral gene delivery vector as a model system for wound-healing research

An attractive experimental method to elucidate the role of growth factors a nd cytokines in cutaneous wound healing would be to overexpress or "knock o ut" a molecule using a gene delivery vector and observe the impact on the w ound repair process. As a first step toward developing an adenoviral gene d elivery procedure to study wound repair, the authors injected beta-galactos idase (beta-gal) adenoviruses either subcutaneously or intradermally into t he dorsal skin of 10-day-old postnatal Sprague-Dawley rats. Histological an alysis and beta-gal staining were used to determine the expression and loca lization of the transferred gene. beta-Gal expression was observed as early as day 1 and up to day 7 postintradermal injection and day 9 postsubcutane ous injection, with no obvious inflammatory reaction detected at the inject ion sites. Furthermore, as expected, greater beta-gal expression was observ ed in the dermis of intradermally injected rats compared with the dermis of subcutaneously injected rats. Next, the authors sought to determine whethe r cutaneous wounds would heal before dissipation of the transferred gene. T hey created incisional and excisional wounds on the backs of similar-age ra ts. They found that incisional wounds closed by day 5 postwounding, whereas excisional wounds closed by day 14 postwounding. Their study demonstrated that an adenoviral vector delivered a gene efficiently into newborn rat ski n and maintained the gene expression for at least as long as it would take for an incisional wound to heal. The combined use of newborn rat wound mode ls and an adenoviral vector may provide a useful in vivo system to define t he biological roles of growth factors and cytokines involved in the wound r epair process. These discoveries may lead to the development of gene therap y approaches for abnormal wound healing.