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Stem Cells International
Volume 2016 (2016), Article ID 6429853, 11 pages
http://dx.doi.org/10.1155/2016/6429853
Research Article

p53-Dependent Senescence in Mesenchymal Stem Cells under Chronic Normoxia Is Potentiated by Low-Dose γ-Irradiation

1Institute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764 Neuherberg, Germany
2Chair of Radiation Biology, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany
3Research Group Clinical Biochemistry, Medical Clinic and Polyclinic IV, Medical Center of the University of Munich, Schillerstraße 42, 80336 Munich, Germany

Received 31 July 2015; Accepted 2 November 2015

Academic Editor: Jane Synnergren

Copyright © 2016 Ines Höfig et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Mesenchymal stem cells (MSCs) are a source of adult multipotent cells important in tissue regeneration. Murine MSCs are known to proliferate poorly in vitro under normoxia. The aim of this study is to analyze the interaction of nonphysiological high oxygen and low-dose γ-irradiation onto growth, senescence, and DNA damage. Tri-potent bone marrow-derived MSCs from p53 wildtype and p53−/− mice were cultured under either 21% or 2% O2. Long-term observations revealed a decreasing ability of wildtype mMSCs to proliferate and form colonies under extended culture in normoxia. This was accompanied by increased senescence under normoxia but not associated with telomere shortening. After low-dose γ-irradiation, the normoxic wildtype cells further increased the level of senescence. The number of radiation-induced γH2AX DNA repair foci was higher in mMSCs kept under normoxia but not in p53−/− cells. P53-deficient MSCs additionally showed higher clonogeneity, lower senescence levels, and fewer γH2AX repair foci per cell as compared to their p53 wildtype counterparts irrespective of oxygen levels. These results reveal that oxygen levels together with γ-irradiation and p53 status are interconnected factors modulating growth capacity of BM MSCs in long-term culture. These efforts help to better understand and optimize handling of MSCs prior to their therapeutic use.