Mesenchymal Stem Cells Transduced by Vascular Endothelial Growth Factor Gene for Ischemic Random Skin Flaps

Abstract

Vascular endothelial growth factor (VEGF) plays an important role in inducing angiogenesis. Mesenchymal stem cells may have the potential for differentiation into several types of cells, including vascular endothelial cells. In this study, the authors explored the feasibility of applying mesenchymal stem cells transduced by the VEGF gene to the treatment of ischemic random skin flaps. Mesenchymal stem cells were isolated from Sprague-Dawley rat bone marrow and cultured in vitro. Plasmid pcDNA3.1(-)/VEGF165 containing the VEGF gene was transduced into the mesenchymal stem cells by liposome. The mesenchymal stem cells were stained with chloromethyl-1-1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanineperchlorate before the transplantation. Thirty rats were randomized into three groups. Groups A, B, and C were injected with mesenchymal stem cells transduced with pcDNA3.1(-)/VEGF165 plasmid, mesenchymal stem cells, and medium only, respectively. On the fourth day after injection, random dorsal skin flaps measuring 9 x 2 cm were elevated. The survival, neovascularization, and blood flow recovery of the flaps were detected. VEGF-transduced mesenchymal stem cells expressed VEGF highly in vitro and in vivo. Transplanted mesenchymal stem cells survived and incorporated into the capillary networks in the ischemic rat flaps. The viability measurements showed an increased percentage flap survival in group A (83.1 +/- 2.6 percent) as compared with either group B (66.4 +/- 6.1 percent) or group C (51.5 +/- 7.5 percent) (p < 0.01). The capillary density and the blood perfusion of the flaps in the experimental group were significantly higher than those in the other two groups (p < 0.01). VEGF-transduced mesenchymal stem cells can increase ischemic flap neovascularization and augment the surviving areas.