Shortening of human cell life span by induction of p16ink4a through the platelet-derived growth factor receptor β
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...
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Published in | Journal of cellular physiology Vol. 221; no. 2; pp. 335 - 342 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.11.2009
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | istex:4A9EFFF753DE5301762E9B795DF64235E79A7341 ark:/67375/WNG-8RSQ7NL4-P ArticleID:JCP21860 Grant for Child Health and Development - No. H15C-2 Ministry of Education, Culture, Sports, Science and Technology of Japan - No. KAKENHI 14657051 Japan Health Sciences Foundation - No. KH71064 The Research Grant for Cardiovascular Diseases - No. H16C-6 Hidekazu Takahashi, Masashi Toyoda, and Jun-ichi Birumachi contributed equally to this work. Hidekazu Takahashi, Masashi Toyoda, and Jun‐ichi Birumachi contributed equally to this work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9541 1097-4652 |
DOI: | 10.1002/jcp.21860 |