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Shortening of human cell life span by induction of p16ink4a through the platelet‐derived growth factor receptor β
Author(s) -
Takahashi Hidekazu,
Toyoda Masashi,
Birumachi Junichi,
Horie Akane,
Uyama Taro,
Miyado Kenji,
Matsumoto Kenji,
Saito Hirohisa,
Umezawa Akihiro
Publication year - 2009
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21860
Subject(s) - mesenchymal stem cell , microbiology and biotechnology , growth factor , biology , basic fibroblast growth factor , fibroblast growth factor , stem cell , platelet derived growth factor receptor , epidermal growth factor , cell growth , cell culture , cancer research , receptor , biochemistry , genetics
Mesenchymal stem cells (MSCs) are attracting a great deal of attention because they represent a valuable source of cells for use in regenerative medicine. In human cell culture it is important to obtain large numbers of cells for use in therapy. In this study, we attempted to prolong life span of a marrow‐derived mesenchymal stem cell using a combination of growth factors and hormones. Furthermore we tested whether chemically defined culture conditions are sufficient for maintenance of multipotent mesenchymal stem cells. Epidermal growth factor, platelet‐derived growth factor‐BB (PDGF‐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. J. Cell. Physiol. 221: 335–342, 2009. © 2009 Wiley‐Liss, Inc.