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The Role of Low-Dose Radiation in Association with TNF-α on Immunomodulatory Properties of Mesenchymal Stem Cells

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Abstract

Ionizing radiation (IR) is an important medical tool. Despite the effects associated with high-dose radiation during or after treatment, as well as in accidental exposures, the direct or indirect effect of low-dose IR in cells remain poorly documented. IR can affect the tissue microenvironment, including mesenchymal stem cells (MSCs), which have high regenerative and immunomodulatory capacities. This study aimed to investigate the effect of low-dose IR in association with the inflammatory stimuli of TNF-α on the immunomodulatory capacity of MSCs. MSCs were irradiated with a low-dose IR, stimulated with TNF-α, and cultivated in a bystander system with murine spleen cells. The results showed that TNF-R1 is expressed in MSCs and is not affected, even in irradiated MSCs. However, irradiated MSCs produced reduced amounts of IL-6 and increased amounts of IL-10. The levels of PGE2 and NO• in MSCs were also increased when stimulated with TNF-α. Furthermore, conditioned media from irradiated MSCs reduced the proliferation of bystander lymphocytes and reduced the metabolic activity of macrophages. In addition, conditioned media from irradiated MSCs modulated the profile of cytokines in bystander spleen cells (lymphocytes and macrophages), reducing inflammatory and increasing anti-inflammatory cytokines, also increasing Treg cells. In conclusion, low-dose IR in association with an inflammatory stimulus affects the immunomodulatory properties of MSCs. In this way, the immunosuppressive capability of MSCs can be explored for several disease treatments where IR usually part of the context of the treatment. However, a complete understanding of the mechanisms underlying these interactions need further investigation.

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Acknowledgments

This work was supported by grants from the Fundação de Amparo a Pesquisa do Estado de São Paulo – FAPESP (grant number: 2018/25813-8). Fock RA is fellow of the Conselho Nacional de Pesquisa e Tecnologia (CNPq).

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  1. Laboratory of Experimental Haematology, Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, Avenida Lineu Prestes, 580, Bloco 17, São Paulo, SP, Brazil

    Amanda Nogueira-Pedro, Edson Naoto Makiyama & Ricardo Ambrósio Fock

  2. Department of Clinical and Experimental Oncology, Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil

    Helena Regina Comodo Segreto

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  1. Amanda Nogueira-Pedro
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Nogueira-Pedro, A., Makiyama, E.N., Segreto, H.R.C. et al. The Role of Low-Dose Radiation in Association with TNF-α on Immunomodulatory Properties of Mesenchymal Stem Cells. Stem Cell Rev and Rep 17, 968–980 (2021). https://doi.org/10.1007/s12015-020-10084-9

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