The replicative senescent mesenchymal stem / stromal cells defect in DNA damage response and anti-oxidative capacity

International Journal of Medical Sciences
Jin YuJin Yang

Abstract

Replicative senescence and potential malignant transformation are great limitations in the clinical application of bone marrow-derived mesenchymal stem / stromal cells (MSCs). An abnormal DNA damage response may result in genomic instability, which is an integral component of aging and tumorigenesis. However, the effect of aging on the DNA damage response in MSCs is currently unknown. In the present study, we evaluated the DNA damage response induced by oxidative stress and DNA double-strand breaks in human bone marrow-derived MSCs. After long-term cell culture, replicative senescent MSCs (sMSCs) were characterized by a poor proliferation rate, high senescence-associated β-galactosidase activity, and enhanced expression of P53 and P16. Features of the DNA damage response in these sMSCs were then compared with those from early-passage MSCs. The sMSCs were more sensitive to hydrogen peroxide and bleomycin treatment with respect to cell viability and apoptosis induction. Combined with the comet assay, γH2AX foci characterization and reactive oxygen species detection were used to demonstrate that the antioxidant and DNA repair ability of sMSCs are attenuated. This result could be explained, at least in part, by the downregulation o...Continue Reading

Citations

Jan 15, 2019·Current Rheumatology Reports·Lin GaoR John Looney
Jul 22, 2019·Human Genetics·Taylor McNeelyIsabel Beerman
Oct 10, 2020·World Journal of Stem Cells·Qing-Shu MengXiao-Ting Liang
Oct 30, 2020·ACS Applied Materials & Interfaces·Eleana SomvilleKarine Glinel
Dec 17, 2021·Stem Cells and Development·Xunhui GuoJing Liu

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Methods Mentioned

BETA
light microscopy
PCR
electrophoresis
fluorescence
flow cytometry
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ImageJ

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