Platelet factors stimulate fibroblasts and smooth muscle cells quiescent in plasma serum to proliferate

Whole blood serum is widely recognized as essential for the growth of diploid cells in culture. Dermal fibroblasts and arterial smooth muscle cells fail to proliferate in culture in the presence of serum derived from platelet-poor plasma. Platelet-poor plasma serum is capable of maintaining monkey arterial smooth muscle cells quiescent in culture at either low (1.5 X 10(3)) or high (2.0 X 10(4)) population densities. The proportion of cells traversing the cell cycle under these conditions was approximately 3 percent. Equal numbers of quiescent smooth muscle cells initiated DNA synthesis and cell division when treated with whole blood serum or with an equivalent quantity of platelet-poor plasma serum supplemented with a factor(s) derived from a supernate obtained after exposure of human platelets to purified thrombin in vitro. Exposure of quiescent cells to 5 percent whole blood serum or 5 percent platelet-poor plasma serum plus 5 μg/ml of crude platelet factor(s) preparations for 1 h stimulated as many cells to initiate DNA synthesis as did exposure for 24 hr, and was independent of the cell densities used in these experiments. Thus, one of the principal mitogens for fibroblasts and for arterial smooth muscle cells in culture present in all blood sera thus far examined appears to be derived from platelets. The system of diploid fibroblasts or smooth muscle cells grown in serum lacking platelet factor(s) permits one to use cells quiescent in the presence of optimal levels of serum and of the low molecular weight components of the defined medium for the study of growth control in culture. This system also permits the study of smooth muscle proliferation as it may relate to the proliferative response observed in atherogenesis in vivo.