Cellular and physiologic effects of exogenous liposomal IGF-1 cDNA gene transfer in acute wounds

The purpose of the present study was to examine the molecular interactions after liposomal cDNA gene transfer and whether the exogenous gene transfer is recognized by the cell and causes endogenous cellular and physiologic responses. Insulin-like growth factor-I (IGF-I) is known to cause, when administered as a protein, adverse side effects, due to lack of cellular responses. Therefore, we used IGF-I cDNA as a vector to study cellular and physiological effects after liposomal administration in an acute wound. Sprague-Dawley rats were inflicted an acute wound and divided into two groups to receive weekly subcutaneous injections of liposomes plus the Lac-Z gene (0.2 μg, vehicle), or liposomes plus the IGF-I cDNA (2.2 μg) and Lac Z gene (0.22 μg). Transfection was confirmed by histochemical assays for β-galactosidase. Planimetry, immunological assays, and histological and immunohistochemical techniques were used to determine molecular mechanisms after gene transfer, protein expression, and dermal and epidermal regeneration. IGF-I cDNA transfer increased IGF-I protein expression and caused concomitant cellular responses by increasing IGFBP-3 and decreasing IGFBP-1. IGF-I cDNA transfer increased IGF-I, FGF, KGF, and PDGF protein concentration, while it had no effect on TGF-β. IGF-I cDNA exerted promitogenic anti-apoptotic effects on basal keratinocytes, thus improving epidermal regeneration. IGF-I cDNA improved dermal regeneration by an increased collagen IV deposition. IGF-I cDNA increased VEGF concentrations and thus neovascularization. Exogenous administered IGF-I cDNA is recognized by the cell and leads to similar intracellular responses as the endogenous gene. Liposomal IGF-I gene transfer further leads to improved dermal and epidermal regeneration by interacting with other growth factors.