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

• Published in: Biology bulletin of the Russian Academy of Sciences Vol. 48; no. 11; pp. 2060 - 2070
• Main Authors: Rodina, A. V., Semochkina, Y. P., Vysotskaya, O. V., Glukhov, A. I., Moskaleva, E. Yu
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.12.2021; Springer Nature B.V
• Subjects: Adipose tissue; Biochemistry; Biomedical and Life Sciences; Body fat; Cell Biology; Cell cycle; Cytokines; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; Double-strand break repair; Ecology; Ionizing radiation; Life Sciences; Mesenchymal stem cells; Modification of Radiation Effects; Radiation; Radiation therapy; Radiosensitivity; Stem cells; Telomerase; Zoology; γ Radiation; mesenchymal stem cells; radiosensitivity; adipose tissue; γ-radiation; DNA double-strand breaks; γН2АХ; low doses
• ISSN: 1062-3590; 1608-3059
• DOI: 10.1134/S1062359021110078

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 G 0 /G 1 arrest after 24 h, but G 2 /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.