EVIDENCE FOR CULTURED HUMAN VASCULAR SMOOTH-MUSCLE CELL HETEROGENEITY- ISOLATION OF CLONAL CELLS AND STUDY OF THEIR GROWTH-CHARACTERISTICS

The monoclonal theory of atherosclerosis postulates that the initial v ascular smooth muscle cell (VSMC) proliferative event involves the exp ansion of a single cell or a sub-population of cells thus implying dif ferences in the replicative potential of VSMC. Using the technique of limited dilution, VSMC clones derived from animal tissues have been pr eviously isolated and shown to be morphologically heterogeneous. Howev er, the same technique applied to human VSMC (HVSMC) has been unsucces sful, possibly because HVSMC do not grow when plated at very low densi ties. In this report, the anchorage-independent growth of HVSMC in sem i-solid medium was studied. Platelet-derived growth factor-BB (PDGF-BB ) and to a lesser extent PDGF-AB and basic fibroblast growth factor (b FGF) induced colony formation. This assay provided a tool for the isol ation of HVSMC clones. In terms of their growth characteristics and re sponsiveness to several growth factors, isolated HVSMC clones and the original parental cell population exhibited marked heterogeneity.