Enhanced angiogenesis in grafted skins by laser-induced stress wave-assisted gene transfer of hepatocyte growth factor

Treatment to increase secretion of growth factors related to angiogenesis by gene transfection is a promising therapeutic solution for improving the outcome of tissue transplantation. We attempted to deliver a therapeutic vector construct carrying the human hepatocyte growth factor (hHGF) gene to skin grafts of rats using laser-induced stress waves (LISWs), with the objective of enhancing their adhesion. First we delivered the hHGF gene to rat native skin in vivo to determine the optimum gene transfer conditions. We then transferred the hHGF gene to excised rat skins, with which autografting was performed. We found that the density and uniformity of neovascularities were significantly enhanced in the grafted skins that were transfected using LISWs. These results suggest the efficacy of this method to improve the outcome of skin grafting. To our knowledge, this is the first experimental demonstration of a therapeutic efficacy based on LISW-mediated gene transfection. Since the present method can be applied not only to various types of tissues but also to bioengineered tissues, this technique has the potential to contribute to progress in transplantation medicine and future regenerative medicine.