Archives → 2019 → Vol. 59, No. 3 → pp. 243-254
Article
Features of Long-term Cultured Adipose Tissue-derived Mesenchymal Stem Cells Response to γ-Irradiation
Rodina A.V., Semochkina Y.P., Vysotskaya O.V., Glukhov A.I., Moskaleva E. Yu.
National Research Center “Kurchatov Institute”, Moscow, Russia
Abstract
Tissue regeneration following radiotherapy is due to the survival and regenerative abilities of tissue stem cells and resident or invading mesenchymal stem cells (MSCs), and their functional characteristics significantly depend on the sensitivity to ionizing radiation. The aim of the work was to study the effect of long-term cultivation adipose tissue-derived MSCs on their radiosensitivity and the ability to DNA double-strand break (DSB) repair. 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 MSCs cultures and analyzed their radiosensitivity at early and late passages. MSCs possessed a high telomerase activity at passage 6 (P6) and extremely low at passage 30 (P30). The doubling time of cells decreased by 7 hours to passage 30. MSC irradiated at P30 demonstrated significantly decreased survival 7 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. MSCs cell cycle analysis at P30 and P6 indicated G0/G1 arrest after 24 hours, but G2/M arrest at 6 Gy after 7 days. The P30 MSCs were able to efficiently repair DNA DSB 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, possess stable functional characteristics and differentiation potential after irradiation, suggesting their resistance to sublethal doses of γ-radiation, and can retain their functions in the tissue surrounding irradiated organ.
Keywords
mesenchymal stem cells, adipose tissue, DNA double-strand breaks, γ-radiation, radiosensitivity, low doses
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