Development of the Adaptive Response and Bystander Effect Induced by Low-Dose Ionising Radiation in Human Mesenchymal Stem Cells

2010 ◽  
pp. 225-231
Author(s):  
Aleksey V. Ermakov ◽  
Marina S. Konkova ◽  
Svetlana V. Kostyuk ◽  
Tatjana D. Smirnova ◽  
Liudmila V. Efremova ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adaptive Response ◽  
Low Dose ◽  
Bystander Effect ◽  
Human Mesenchymal Stem Cells ◽  
Ionising Radiation

Photo biostimulatory effect of low dose photodynamic therapy on human mesenchymal stem cells

2020 ◽  
Vol 31 ◽  
pp. 101886
Author(s):  
Reza Fekrazad ◽  
Sohrab Asefi ◽  
Khatereh Khorsandi ◽  
Marzieh Nejatifard
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Photodynamic Therapy ◽  
Low Dose ◽  
Human Mesenchymal Stem Cells

Analysis of the Effects of Low-Dose Radiation on Human Mesenchymal Stem Cells

2021 ◽  
Vol 65 (6) ◽  
pp. 5-10
Author(s):  
D. Usupzhanova ◽  
T. Astrelina ◽  
I. Kobzeva ◽  
V. Nikitina ◽  
Yu. Suchkova ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Adaptive Response ◽  
Proliferative Activity ◽  
Human Mesenchymal Stem Cells ◽  
Conditioned Media ◽  
X Ray ◽  
Cultivation In Vitro

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.

scholarly journals Effect of Low-Dose Ionizing Radiation on the Expression of Mitochondria-Related Genes in Human Mesenchymal Stem Cells

2021 ◽  
Vol 23 (1) ◽  
pp. 261
Author(s):  
Svetlana V. Kostyuk ◽  
Elena V. Proskurnina ◽  
Marina S. Konkova ◽  
Margarita S. Abramova ◽  
Andrey A. Kalianov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ionizing Radiation ◽  
Low Dose ◽  
Human Mesenchymal Stem Cells ◽  
Mitochondrial Respiratory Chain ◽  
Respiratory Chain Complexes ◽  
Cell Free Dna ◽  
X Ray ◽  
Free Dna

The concept of hormesis describes a phenomenon of adaptive response to low-dose ionizing radiation (LDIR). Similarly, the concept of mitohormesis states that the adaptive program in mitochondria is activated in response to minor stress effects. The mechanisms of hormesis effects are not clear, but it is assumed that they can be mediated by reactive oxygen species. Here, we studied effects of LDIR on mitochondria in mesenchymal stem cells. We have found that X-ray radiation at a dose of 10 cGy as well as oxidized fragments of cell-free DNA (cfDNA) at a concentration of 50 ng/mL resulted in an increased expression of a large number of genes regulating the function of the mitochondrial respiratory chain complexes in human mesenchymal stem cells (MSC). Several genes remained upregulated within hours after the exposure. Both X-ray radiation and oxidized cfDNA resulted in upregulation of FIS1 and MFN1 genes, which regulated fusion and fission of mitochondria, within 3–24 h after the exposure. Three hours after the exposure, the number of copies of mitochondrial DNA in cells had increased. These findings support the hypothesis that assumes oxidized cell-free DNA as a mediator of MSC response to low doses of radiation.

Preclinical Safety Evaluation of Human Mesenchymal Stem Cell Transplantation in Cerebrum of Nonhuman Primates

2014 ◽  
Vol 33 (5) ◽  
pp. 403-411 ◽  
Author(s):  
Ming Feng ◽  
Yan Li ◽  
Qin Han ◽  
Xinjie Bao ◽  
Ming Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Clinical Application ◽  
Low Dose ◽  
Human Mesenchymal Stem Cells ◽  
High Dose ◽  
Mesenchymal Stem Cell Transplantation

The efficacy of stem cell transplantation for promoting recovery of patients with neurological diseases, such as stroke, has been reported in several studies. However, the safety of the intracerebral transplantation of human mesenchymal stem cells (hMSCs) remains unclear. The aim of the study was to evaluate the safety of hMSCs transplanted in cerebrum of Macaca fascicularis and to provide evidence for clinical application. A total of 24 M fascicularis were assigned to 3 groups randomly: low dose (3.0 × 105 cells/kg), high dose (2.5 × 106 cells/kg), and the control (normal saline [NS]). Human mesenchymal stem cells or NS were injected into each monkey for 2 times, with an interval of 3 weeks. The injection point was located outside of the right putamen, according to a stereotactic map and preoperative magnetic resonance imaging of the monkeys. Animal health, behavior, biophysical and biochemical parameters, and brain neurological function were routinely monitored over a 6-month period posttransplantation, and the histopathologic examinations were also performed. The results showed that local pathologic damage including local tissue necrosis and inflammation was induced after the injection. The damage of low-dose and high-dose groups was greater than that of the control group, yet over time, the damage could be repaired gradually. No major hMSCs-associated changes were induced from other indicators, and the transplantation of hMSCs in monkeys did not affect total immunoglobulin (Ig) M, total IgG, CD3, CD4, or CD8 values. We therefore conclude that transplantation of hMSCs to the cerebrum represents a safe alternative for clinical application of neurological disorders.

scholarly journals Low-Dose Ionizing γ-Radiation Promotes Proliferation of Human Mesenchymal Stem Cells and Maintains Their Stem Cell Characteristics

2017 ◽  
Vol 14 (4) ◽  
pp. 421-432 ◽  
Author(s):  
Wheemoon Cho ◽  
E Ske Kim ◽  
Chang Mo Kang ◽  
Young-Hoon Ji ◽  
Jong-Il Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Low Dose ◽  
Human Mesenchymal Stem Cells ◽  
Γ Radiation

scholarly journals Formation of γH2AX and pATM Foci in Human Mesenchymal Stem Cells Exposed to Low Dose-Rate Gamma-Radiation

2019 ◽  
Vol 20 (11) ◽  
pp. 2645 ◽  
Author(s):  
Stepan Ulyanenko ◽  
Margarita Pustovalova ◽  
Sergey Koryakin ◽  
Evgenii Beketov ◽  
Anatolii Lychagin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gamma Radiation ◽  
Dose Rate ◽  
Low Dose ◽  
Human Mesenchymal Stem Cells ◽  
Linear Dose ◽  
Low Dose Rate ◽  
Acute Irradiation ◽  
Non Linear

DNA double-strand breaks (DSB) are among the most harmful DNA lesions induced by ionizing radiation (IR). Although the induction and repair of radiation-induced DSB is well studied for acute irradiation, responses to DSB produced by chronic IR exposures are poorly understood, especially in human stem cells. The aim of this study was to examine the formation of DSB markers (γH2AX and phosphorylated kinase ATM, pATM, foci) in human mesenchymal stem cells (MSCs) exposed to chronic gamma-radiation (0.1 mGy/min) in comparison with acute irradiation (30 mGy/min) at cumulative doses of 30, 100, 160, 240 and 300 mGy. A linear dose-dependent increase in the number of both γH2AX and pATM foci, as well as co-localized γH2AX/pATM foci (“true” DSB), were observed after an acute radiation exposure. In contrast, the response of MSCs to a chronic low dose-rate IR exposure deviated from linearity towards a threshold model, for γH2AX, pATM foci and γH2AX/pATM foci, with an indication of a “plateau”. The state of equilibrium between newly formed DSB at a low rate during the protracted exposure time and the elimination of a fraction of DSB is proposed as a mechanistic explanation of the non-linear DSB responses following a low dose-rate irradiation. This notion is supported by the observation of the elimination of a substantial fraction of DSB 6 h after the cessation of the exposures. Our results demonstrate non-linear dose responses for γH2AX and pATM foci in human MSCs exposed to low dose-rate IR and showed the existence of a threshold, which may have implications for radiation protection in humans.

scholarly journals The response of human mesenchymal stem cells to internal exposure to tritium β-rays

2019 ◽  
Vol 60 (4) ◽  
pp. 476-482 ◽  
Author(s):  
Yi Quan ◽  
Jinxian Lin ◽  
Bing Deng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cellular Response ◽  
Low Dose ◽  
Biological Effects ◽  
Tritiated Water ◽  
Human Mesenchymal Stem Cells ◽  
Internal Exposure ◽  
Low Dose Radiation ◽  
Dose Radiation

Abstract There is no doubt that estimating the exposure risk of external and internal low-dose radiation is an imperative issue in radiobiological study. Human mesenchymal stem cells (hMSCs) are multipotent and self-renewing, supporting the regeneration of damaged tissue, including tissue damaged by radiation. However, the responses of hMSCs to internal exposure to radionuclides are still insufficiently understood. In order to evaluate the adverse effects produced by internal exposure to tritiated water (HTO) at a low dose, hMSCs were exposed to 2 × 107 Bq/ml HTO, and the biological effects after the exposure were examined. Apoptosis and DNA double-strand breaks (DSBs) were assayed to analyze the cellular response to the damage induced by HTO. Slight enhancement of apoptosis was found after treatment, except at the dose of 9 mGy. The number of DSBs at 24 h post-irradiation showed that the DNA damage was able to be efficiently repaired by the hMSCs. Moreover, the increasing proportion of the cell population in S phase proved that the persistence of residual γH2AX foci at lower concentrations of HTO was attributable to the secondary production of DSBs in DNA replication. Our work adds to the available data, helping us understand the risk of stem cell transformation due to internal exposure and its correlation with low-dose radiation–induced carcinogenesis.

scholarly journals Low-Dose Ionizing Radiation Affects Mesenchymal Stem Cells via Extracellular Oxidized Cell-Free DNA: A Possible Mediator of Bystander Effect and Adaptive Response

2017 ◽  
Vol 2017 ◽  
pp. 1-22 ◽  
Author(s):  
V. A. Sergeeva ◽  
E. S. Ershova ◽  
N. N. Veiko ◽  
E. M. Malinovskaya ◽  
A. A. Kalyanov ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ionizing Radiation ◽  
Adaptive Response ◽  
Low Dose ◽  
Low Doses ◽  
Dna Breaks ◽  
Cell Free Dna ◽  
Free Dna

We have hypothesized that the adaptive response to low doses of ionizing radiation (IR) is mediated by oxidized cell-free DNA (cfDNA) fragments. Here, we summarize our experimental evidence for this model. Studies involving measurements of ROS, expression of the NOX (superoxide radical production), induction of apoptosis and DNA double-strand breaks, antiapoptotic gene expression and cell cycle inhibition confirm this hypothesis. We have demonstrated that treatment of mesenchymal stem cells (MSCs) with low doses of IR (10 cGy) leads to cell death of part of cell population and release of oxidized cfDNA. cfDNA has the ability to penetrate into the cytoplasm of other cells. Oxidized cfDNA, like low doses of IR, induces oxidative stress, ROS production, ROS-induced oxidative modifications of nuclear DNA, DNA breaks, arrest of the cell cycle, activation of DNA reparation and antioxidant response, and inhibition of apoptosis. The MSCs pretreated with low dose of irradiation or oxidized cfDNA were equally effective in induction of adaptive response to challenge further dose of radiation. Our studies suggest that oxidized cfDNA is a signaling molecule in the stress signaling that mediates radiation-induced bystander effects and that it is an important component of the development of radioadaptive responses to low doses of IR.

Sign in / Sign up

Export Citation Format

Share Document