Cell-mediated delivery of fibroblast growth factor-2 and vascular endothelial growth factor onto the chick chorioallantoic membrane: Endothelial fenestration and angiogenesis

Fibroblast growth factor-2 (FGF2) and vascular endothelial growth factor (V EGF) exert their angiogenic activity by interacting with endothelial cells in a distinct manner. In this study, we investigated the morphological feat ures of endothelial cells of the chick embryo chorioallantoic membrane (CAM ) microvasculature after stimulation with FGF2 or VEGF. In order to provide a continuous delivery of the growth factor, we utilized a recently develop ed gelatin sponge/CAM assay in which a limited number of FGF2- or VEGF-tran sfected cells were adsorbed onto gelatin sponges and applied on the top of the CAM on day 8 of development. Their angiogenic activity was compared to that exerted by a single bolus of the corresponding growth factor. All the angiogenic stimuli induced a comparable vasoproliferative response, as demo nstrated by the appearance of similar numbers of immature blood vessels wit hin the sponge on day 12. No angiogenic response was observed in CAMs impla nted with the corresponding parental cell lines or vehicle. Electron micros copy demonstrated that VEGF-overexpressing cells modified the phenotype of the endothelium of the blood vessels at the boundary between the implant an d the surrounding CAM mesenchyme. The endothelial lining of 30% of these ve ssels showed segmental attenuations, was frequently interrupted and became fenestrated, mimicking what is observed in tumor vasculature. In contrast, the vessels consisted of continuous endothelium sealed by tight junctions i n all the other experimental conditions. These results indicate that FGF2 a nd VEGF interact with endothelial cells of the CAM in a distinct manner. Bo th growth factors induce a potent angiogenic response, but only VEGF delive red in a continuous manner by its transfectants can modify the phenotype of the otherwise quiescent endothelium of CAM blood microvessels. The gelatin sponge/CAM assay may constitute a new model to study the mechanisms leadin g to endothelial fenestration in tumor growth. Copyright (C) 2001 S. Karger AG, Basel.