Human endothelial cell migration. Stimulation by a released platelet factor

The relative contribution of migration and proliferation to the process of endothelial repair has been studied in vitro using a quantitative assay of human endothelial cell migration. In this method surface coverage by radial migration of cells from a circular monolayer toward nonendothelialized adjacent surface under an agarose gel is determined independently of proliferation by comparing surface coverage by irradiated and nonirradiated cells. In the nonirradiated cultures, outward cell movement during the first 24 hr decreases cell density in the monolayer center followed by a burst of proliferation that is inversely related to cell density. However, cells at the advancing margin maintain a low proliferative rate to cell density ratio. Irradiated endothelial cells achieve the same surface coverage as the nonirradiated cells during the first 3 days of culture. A nondialyzable, heat-stable factor released from platelets doubles the rate of irradiated endothelial cell surface coverage. In contrast, fibroblast growth factor, medium conditioned by cultured human macrophages, and zymosan-treated fresh human serum do not augment endothelial cell migration. These data indicate that migration is the principal early mechanism by which endothelial cells cover adjacent surfaces in culture and that this process is enhanced by a releasable platelet constituent.