p53-Dependent Senescence in Mesenchymal Stem Cells under Chronic Normoxia Is Potentiated by Low-Dose γ-Irradiation
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, sen...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/6429853 |
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| author | Ines Höfig Yashodhara Ingawale Michael J. Atkinson Heidi Hertlein Peter J. Nelson Michael Rosemann |
| author_facet | Ines Höfig Yashodhara Ingawale Michael J. Atkinson Heidi Hertlein Peter J. Nelson Michael Rosemann |
| author_sort | Ines Höfig |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-854087b1c0cf45c68616f675174295c1 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-854087b1c0cf45c68616f675174295c12025-02-03T06:07:11ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/64298536429853p53-Dependent Senescence in Mesenchymal Stem Cells under Chronic Normoxia Is Potentiated by Low-Dose γ-IrradiationInes Höfig0Yashodhara Ingawale1Michael J. Atkinson2Heidi Hertlein3Peter J. Nelson4Michael Rosemann5Institute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764 Neuherberg, GermanyInstitute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764 Neuherberg, GermanyInstitute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764 Neuherberg, GermanyInstitute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764 Neuherberg, GermanyResearch Group Clinical Biochemistry, Medical Clinic and Polyclinic IV, Medical Center of the University of Munich, Schillerstraße 42, 80336 Munich, GermanyInstitute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764 Neuherberg, GermanyMesenchymal 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.http://dx.doi.org/10.1155/2016/6429853 |
| spellingShingle | Ines Höfig Yashodhara Ingawale Michael J. Atkinson Heidi Hertlein Peter J. Nelson Michael Rosemann p53-Dependent Senescence in Mesenchymal Stem Cells under Chronic Normoxia Is Potentiated by Low-Dose γ-Irradiation Stem Cells International |
| title | p53-Dependent Senescence in Mesenchymal Stem Cells under Chronic Normoxia Is Potentiated by Low-Dose γ-Irradiation |
| title_full | p53-Dependent Senescence in Mesenchymal Stem Cells under Chronic Normoxia Is Potentiated by Low-Dose γ-Irradiation |
| title_fullStr | p53-Dependent Senescence in Mesenchymal Stem Cells under Chronic Normoxia Is Potentiated by Low-Dose γ-Irradiation |
| title_full_unstemmed | p53-Dependent Senescence in Mesenchymal Stem Cells under Chronic Normoxia Is Potentiated by Low-Dose γ-Irradiation |
| title_short | p53-Dependent Senescence in Mesenchymal Stem Cells under Chronic Normoxia Is Potentiated by Low-Dose γ-Irradiation |
| title_sort | p53 dependent senescence in mesenchymal stem cells under chronic normoxia is potentiated by low dose γ irradiation |
| url | http://dx.doi.org/10.1155/2016/6429853 |
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