Mesenchymal Stem Cells Early Response to Low-Dose Ionizing Radiation

Abstract

IntroductionMesenchymal stem cells (MSCs) are applied as the therapeutic agents, e.g., in the tumor radiation therapy.Purpose of the StudyTo evaluate the human adipose MSC early response to low-dose ionizing radiation (LDIR).Materials and MethodsWe investigated different LDIR (3, 10, and 50 cGy) effects on reactive oxygen species production, DNA oxidation (marker 8-oxodG), and DNA breaks (marker ɣ H2AX) in the two lines of human adipose MSC. Using reverse transcriptase–polymerase chain reaction, fluorescence-activated cell sorting, and fluorescence microscopy, we determined expression of genes involved in the oxidative stress development (NOX4), antioxidative response (NRF2), antiapoptotic and proapoptotic response (BCL2, BCL2A1, BCL2L1, BIRC2, BIRC3, and BAX1), in the development of the nuclear DNA damage response (DDR) (BRCA1, BRCA2, ATM, and P53). Cell cycle changes were investigated by genes transcription changes (CCND1, CDKN2A, and CDKN1A) and using proliferation markers KI-67 and proliferating cell nuclear antigen (PCNA).ResultsFifteen to 120 min after exposure to LDIR in MSCs, transient oxidative stress and apoptosis of the most damaged cells against the background of the cell cycle arrest were induced. Simultaneously, DDR and an antiapoptotic response were found in other cells of the population. The 10-cGy dose causes the strongest and fastest DDR following cell nuclei DNA damage. The 3-cGy dose induces a less noticeable and prolonged response. The maximal low range dose, 50 cGy, causes a damaging effect on the MSCs.ConclusionTransient oxidative stress and the death of a small fraction of the damaged cells are essential components of the MSC population response to LDIR along with the development of DDR and antiapoptotic response. A scheme describing the early MSC response to LDIR is proposed.