Expression of vascular endothelial growth factor promotes colonization, vascularization, and growth of transplanted...

A complex vascular network forms an important component of the liver architecture. This network is essential for the supply of oxygen and nutrients to cells and delivery of molecules for metabolic exchange. In this study, we attempted to construct a vascular network in transplanted hepatic tissues and examined the effect of such network on tissue formation. Primary hepatocytes of adult mice were transfected with vascular endothelial growth factor (VEGF) gene in vitro then transplanted with collagen beads intraperitoneally in mice. VEGF-transfected hepatocytes secreted sufficient protein of the transgene in vitro to induce proliferation of endothelial cells. In vivo, VEGF-transfected hepatocytes formed a large number of colonies and developed a significant vascular network in established tissues compared with control tissues. In addition, hepatocytes of VEGF-transfected, established tissues proliferated and formed a substantial parenchymal region. These hepatocytes were also functional as confirmed by the production of albumin. Our results suggested that VEGF expression conferred not only the formation of a vascular network but also promoted tissue formation. Our study showed that ex vivo gene transfection into hepatocytes is a useful method for the induction of liver reconstitution in vivo.