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Features of the Response of Long-Term Cultured Adipose Tissue–Derived Mesenchymal Stem Cells to γ-Irradiation

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Abstract

Tissue regeneration following radiotherapy occurs due to the survival and regenerative abilities of tissue stem cells and resident or invading mesenchymal stem cells (MSCs), and their functional characteristics depend significantly on their sensitivity to ionizing radiation. The aim of this work was to study the effect of long-term cultivation of adipose tissue–derived MSCs on their radiosensitivity and the ability to repair DNA double-strand breaks (DSBs). To determine whether in vitro expansion influences the sensitivity of MSCs to low and sublethal doses of γ-radiation, we maintained short- and long-term MSC cultures and analyzed their radiosensitivity at early and late passages. MSCs possessed a high telomerase activity at passage 6 (P6) and an extremely low one at passage 30 (P30). The doubling time of cells by passage 30 decreased by 7 h. MSCs irradiated at P30 demonstrated significantly decreased survival seven days after irradiation at 0.1 and 1 Gy compared with the control and P6 cultures. The clonogenic activity of MSCs irradiated at P30 and P6 was the same. MSC cell cycle analysis at P30 and P6 indicated G0/G1 arrest after 24 h, but G2/M arrest at 6 Gy after seven days. The P30 MSCs were able to repair DNA DSB efficiently after γ-irradiation. Even after irradiation at a dose of 6 Gy, P30 MSCs maintained their ability for adipocyte differentiation and cytokine secretion. These results demonstrate that, after long-term cultivation, adipose tissue-derived MSCs maintain the ability to repair DNA DSB and possess stable functional characteristics and differentiation potential after irradiation, suggesting their resistance to sublethal doses of γ-radiation. They can also retain their functions in the tissue surrounding the irradiated organ.

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Funding

This work was supported by the Russian Foundation for Basic Research, project no. 15-29-01234.

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Authors and Affiliations

  1. National Research Center Kurchatov Institute, Moscow, Russia

    A. V. Rodina, Y. P. Semochkina, O. V. Vysotskaya, A. I. Glukhov & E. Yu. Moskaleva

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  1. A. V. Rodina
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  2. Y. P. Semochkina
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  3. O. V. Vysotskaya
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  4. A. I. Glukhov
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  5. E. Yu. Moskaleva
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Correspondence to A. V. Rodina.

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Conflict of interest. The authors declare that they have no conflict of interest.

Statement on the welfare of animals. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Translated by M. Batrukova

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Rodina, A.V., Semochkina, Y.P., Vysotskaya, O.V. et al. Features of the Response of Long-Term Cultured Adipose Tissue–Derived Mesenchymal Stem Cells to γ-Irradiation. Biol Bull Russ Acad Sci 48, 2060–2070 (2021). https://doi.org/10.1134/S1062359021110078

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  • DOI: https://doi.org/10.1134/S1062359021110078

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