Sustained low levels of fibroblast growth factor-1 promote persistent microvascular network formation.
BACKGROUND: Therapeutic neovascularization using high growth factor concentrations may lead to transient vessel formation and abnormal microvascular structure. The goal of this study was to quantify temporal and concentration effects of fibroblast growth factor-1 (FGF-1) on the persistence and morphology of microvascular networks. METHODS: Endothelial cells were incubated in suspension culture forming aggregates that were embedded in fibrin glue (FG) and stimulated with varying concentrations of FGF-1 with of heparin. Capillary networks formed were quantified for 21 days. RESULTS: High FGF-1 concentrations resulted in rapid and intense sprout formation, with excessive branching. At later times, these vessels regressed, with cellular debris in former vessel locations. At later times, the 1-ng/mL group surpassed the high concentration groups with continuous sprout growth and complete FG vascularization by 23 days. CONCLUSION: Sustained low levels of FGF-1 maintained a persistent microvascular network response, whereas higher levels resulted in abnormal phenotype followed by vessel regression.