Adenoviral-mediated gene transfer in wound healing: acute inflammatory response in human skin in the SCID mouse model

The use of an adenoviral vector as a means of therapeutic protein delivery for the treatment of impaired wound healing is a potentially effective appl ication of current gene transfer techniques. This study was designed to inv estigate the ability of adenovirus to mediate gene transfer in healing woun ds in human skin in vivo. The human skin/severe combined immunodeficient mo use chimera model was used to study both the response of human tissue to ad enoviral infection and the nature of the acute inflammatory response. The e ffects of adenoviral infection and transgene expression on the rate and qua lity of human wound healing were then investigated. Cell- and species-speci fic monoclonal antibodies were used to characterize the resident skin cell types participating in wound repair, the inflammatory response, and the pro liferative potential of adenovirus-treated compared to control skin. Our st udies show that, following wounding, normal skin architecture is restored i n the presence of adenoviral infection equivalent to noninfected controls. Despite an increased acute inflammatory response after adenovirus injection , no difference in the healing capabilities of wounded skin was observed, s uggesting that adenovirus-mediated gene transfer for growth factor-mediated acceleration of wound healing may be feasible.