Shortening of human cell life span by platelet-derived growth factor via induction of p16ink4a

Shortening of human cell life span by platelet-derived growth factor via induction of p16ink4a

Cells vary in their requirements in a cell type-specific manner, and cells can therefore be categorized or defined by their requirements. In this study, we attempted to prolong life span of a marrow-derived mesenchymal stem cell using a combination of growth factors and hormones. Epidermal growth factor, platelet-derived growth factor-BB, acidic fibroblast growth factor (FGF), basic FGF, and leukemia inhibitory factor were found to be key factors for the mesenchymal stem cell proliferation. The combination of these growth factors showed extremely strong mitogenic activity, and simultaneously induced the expression of cyclin-dependent kinase inhibitor p16ink4a protein and premature senescence more rapidly than serum-supported culture conditions. The induction of p16ink4a by growth factors was mediated through the mitogen-activated protein kinase (MAPK) cascade. Excess growth stimulation by growth factors was thus one of the culture stress signals and a trigger of premature senescence at least in human cells.