Extracellular matrix regulates cell morphology, proliferation, and tissue formation.

The roles of extracellular matrix (ECM) components such as collagen, elastin, proteoglycan, and adhesive glycoprotein in the regulation of cell morphology, proliferation, and tissue formation were investigated. On a basement membrane gel, the perisinusoidal stellate cells (lipocytes, fat-storing cells, Ito cells) formed a mesh-like structure, proliferated slowly, and synthesized only a small amount of collagen. On polystyrene or type I collagen-coated culture dishes, the stellate cells spread well and extended cellular processes. The stellate cells proliferated better and synthesized more collagen on type I collagen-coated dishes than on polystyrene dishes. Co-cultures of hepatic parenchymal cells and fibroblasts formed a three-dimensional hepatic cord-like architecture in the medium supplemented with a long-acting vitamin C derivative, L-ascorbic acid 2-phosphate (Asc 2-P). Skin fibroblasts formed a three-dimensional dermis-like structure in the medium supplemented with Asc 2-P. Asc 2-P stimulated collagen synthesis of these cells. The stimulative effects of Asc 2-P on tissue formation were suppressed when collagen synthesis in these cells was inhibited. These data indicate that ECM can regulate cell morphology, proliferation and tissue formation. Regulation of cellular functions in other tissues such as mammary gland, thymus and prostate by ECM was also reviewed, and the molecular mechanisms of the regulation are discussed.