Factors affecting the migration and growth of endothelial cells from microvessels of bovine retina.

We have developed a retinal microvessel culture system which permits study of the initial events of endothelial cell activation and migration during the angiogenic response. Enzyme digest experiments indicate that Type IV collagen is the major basement membrane component regulating migration and growth of endothelial cells. Following removal of basement membrane collagen, further cell migration and proliferation require a suitable substrate. Laminin, fibronectin and fibrin(ogen) provide excellent substrates for endothelial cell outgrowths while Type I collagen, even if prepared as a three-dimensional gel, or Type IV collagen fails to promote typical cell growth. In contrast to fibrin and fibronectin, plasmin was a poor substrate for cell outgrowth and it is suggested that cell-associated protease activity may exert a regulatory role over endothelial cell-matrix interactions during cell migration.