Analysis of the Effects of Low-Dose Radiation on Human Mesenchymal Stem Cells
Abstract and keywords
Abstract (English):
Purpose: The aim of the study was to study the effect of low X-ray doses on human mesenchymal stem cells (MSCs) in long-term cultivation in vitro. Material and methods: MSCs of the mucosal gum tissue of human were used. Cells were irradiated using an RUST-M1 X-ray unit (Russia) at doses of 50, 80, 100, 250 and 1000 mGy (dose rate40 mGy/min) and then cultivated according to standard methods. Immunological characteristics and viability of MSCs were evaluated on a FACSCanto II flow cytometer (Becton Dickinson CA, USA) for early and late passengers. Proliferative activity (PA) was evaluated using an xCelligence real-time cell analyzer (ACEA Biosciencs, Inc.). Results: It was shown that the proliferative activity (PA) of MSCs of the mucosal gum tissue which were irradiated at dose 50 mGy is comparable with the control group in long-term cultivation while doses of 100 and 250 mGy showed a decrease of PA. Also non-irradiated MSCs showed a significant decrease of the PA during cultivation in a conditioned medium from cells that received dose of 1000 mGy and an increase of PA during cultivation in a conditioned medium of cells that received doses of 50, 100 and 250 mGy. The cells were previously irradiated at dose 250 mGy showed adaptive response during cultivation in conditioned medium from cells that received dose of 1000 mGy. Сonclusion: The assessment of the effects of low radiation doses was focused on the bystander effect in the presented study. It was noted after adding conditioned media from irradiated cells to previously irradiated and non-irradiated MSCs. The bystander effects for low and high doses are different and their biological meaning requires further study. The phenomenon of adaptive response was shown after addition conditioned media from cells irradiated at dose 1000 mGy to pre-irradiated MSCs received a dose of 250 mGy. The obtained result leads to the conclusion that the effects of low doses can be positive. Thus, the results of study mainly correspond to the threshold nonlinear concept, according to which the effect is not proportional to the received radiation dose.

Keywords:
human stem cells, low doses, X-ray
References

1. Squillaro T, Galano G, De Rosa R, Peluso G, Galderisi U. Concise Review: The Effect of LowDose Ionizing Radiation on Stem Cell Biology: A Contribution to Radiation Risk. Stem Cells. 2018 Aug; 36(8):1146-53.

2. Fazel R, Krumholz HM, Wang Y et al. Exposure to low-dose ionozing radiation from medical imaging procedures. N Engl J Med. 2009; 361:849-57.

3. ICRP. The 2007 Recommendations of the International Commission on Radiological Protection. Vol 103. 2007:1-332.

4. Pustovalova M, Astrelina T, Grekhova A, Vorobyeva N, Tsvetkova A, Nikitina V, et al. Persistent γH2AX foci Induced by Low Dose X-ray Radiation in Bone Marrow Mesenchymal Stem Cells do not Cause Accelerated Senescence in the Progeny of Irradiated Cells. Aging. 2017; 9 (11): 2397-410.

5. Li W, Wang G, Cui J et al. Low-dose radiation (LDR) induces hematopoietic hormesis: LDR-induced mobilization of hematopoietic progenitor cells intooperipheral blood circulation. Exp Hematol. 2004;32:1088-96.

6. Coleman MA, Yin E, Peterson LE, et al. Low-dose irradiation alters the transcript profiles of human lymphoblastoid cells including genes associated with cytogenetic radioadaptive response. Radiat Res. 2005;164:369-82.

7. Tang FR, Loke WK. Molecular mechanisms of low dose ionizing radiation induced hormesis, adaptive responses, radioresistance, bystander effects and genomic instability. Int J Radiat Biol. 2015;91:13-27.

8. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4) 315-17.

9. Mothersill C, Rea D, Wright EG, et al. Individual variation in the production of a `bystander signal' following irradiation ofprimary cultures of normal human urothelium. Carcinogenesis. 2001; 22(9):1465=71.

10. Liang X, So YH, et al. The low-dose ionizing radiation stimulates cell proliferation via activation of the MAPK/ERK pathway in rat cultured mesenchymal stem cells. J Radiat Res. 2011; 52(3):380-6.

11. Bonner WM. Low-dose radiation: thresholds, bystander effects and adaptive responses. Proc Natl Acad Sci USA. 2003;100:4973-75.

12. Mothersill C, Seymour CB. Cell-cell contact during gamma irradiation is not required to induce a bystander effect in normal human keratinocytes: evidence for release during irradiation of a signal controlling survival into the medium. Radiat. Res.1998;149, 256 =62.

Login or Create
* Forgot password?