Gene Therapy Using Hepatocyte Growth Factor Expressing Adenovirus Improves Skin Flap Survival in a Rat Model

Abstract

Hepatocyte growth factor (HGF) is a potent angiogenic factor that can stimulate the production of blood vessels in ischemic tissue. We investigated whether gene therapy using HGF-expressing adenovirus could enhance skin flap survival. Sprague-Dawley rats were randomly divided into three groups. Rats were subdermally injected with HGF-expressing adenovirus (HGF virus group), recombinant HGF (rhHGF group), or phosphate buffered saline (PBS group) 2 days before and immediately after 3 x 9 cm caudal flap elevation. The survival area of the skin flap, the ratio of blood flow, CD31-positive vessels and, VEGF expression were examined. Skin flap viability was significantly increased in the HGF virus group compared to the rhHGF and PBS groups (71.4%+/- 5.9%, 63.8%+/- 6.4%, and 39.2%+/- 13.0%, respectively) (P=0.025). Furthermore, the blood flow ratio was significantly increased in the HGF virus group. In the HGF virus group, the number of CD31-positive vessels and vascular endothelial growth factor (VEGF) expression were significantly increased. Gene therapy using HGF-expressing adenovirus increase VEGF expression, the number of viable capillaries, and blood flow to the flap, thereby improving skin flap survival.