Effects of dual-gene modification on biological characteristics of vascular endothelial cells and their significance as reserving cells for chronic wound repair

Abstract

bFGF is a commonly used and reliable factor for improving chronic wound healing, and hSulf-1 expression is abundant in surrounding cells of chronic wound tissue and vascular endothelial cells, which can reverse the effect of bFGF and inhibit the signalling activity of cell proliferation. In this study, an adenovirus, Ad5F35ET1-bFGF-shSulf1, was designed for establishing the dual-gene modified vascular endothelial cells, which were used as the repair cells for skin chronic wound. Ad5F35ET1-bFGF-shSulf1 infected ECV304 cells in vitro and mediated the overexpression of bFGF and the knockdown of hSulf-1, which effectively activated the AKT and ERK signal transduction pathways, facilitate cell proliferation and migration, with the cell viability to 128.29% at 72 h after infection, compared to 66.65%, 73.74%, 87.63%, 103.14% in the blank control, Ad5F35ET1-EGFP-shNC, Ad5F35ET1-shSulf1, Ad5F35ET1-bFGF groups, respectively. In the rat ear skin injury model, the wound healing was significantly accelerated in the Ad5F35ET1-rbFGF-shrSulf1 group compared to the blank control group (p = 0.0046), Ad5F35ET1-EGFP-shNC group (p = 0.0245), Ad5F35ET1-shrSulf group (p = 0.0426), and Ad5F35ET1-rbFGF group (p = 0.2853). The results demonstrated that this strategy may be a candidate therapy for chronic injury repair.