Archives2019Vol. 59, No. 4pp. 377-387

Article

Specific Features of the Effect Exerted by Irradiated Bone Marrow Mesenchymal Stem Cells on the Production of Cytokines and Reactive Oxygen Species by Macrophages

Agaeva E.V., Petrov V.N., Konoplyannikov A.G., Lepyokhina L.A., Sayapina E.V., Popovkina O.E.

A.F. Tsyb Medical Radiology Center, Affiliated Department of National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Obninsk, Russia

Abstract

In order to increase the efficiency of cell therapy for acute radiation injuries, we conducted comparative stu-dies of the immunomodulating effects of intact and previously exposed to γ-irradiation at doses of 50–500 mGy and 1–10 Gy bone marrow mesenchymal stromal/stem cells (MSCs) of donor patients on the functional activity of macrophages in allogeneic (human blood mononuclear cells/human MSCs) and xenogeneic (mouse peritoneal macrophages/human MSCs) in vitro systems. Tests of zymosan-induced chemiluminescence (CL-activity) and lipopolysaccharide-induced production of cytokines: TNF-&alpha, IFN-&gamma, IL-1α and IL-10 by macrophages were used as criteria. It has been established that intact and gamma-irradiated MSCs, as well as their conditioned media (CM), are characterized by inhibition of the production of reactive oxygen species (ROS), which can play a significant role in the formation of the immunosuppressive microenvironment during MSC transplantation. The impact of low doses of gamma irradiation (50–100 mGy) on MSCs was characterized by a stimulating effect, and high doses of gamma irradiation had an inhibitory effect on the estimated indicators of the functional activity of macrophages as compared to intact MSCs. It is assumed that gamma irradiation at small doses can serve as one of the approaches to the preconditioning of immunomo-dulating and proliferative activity of MSCs.

Keywords

gamma radiation, mesenchyme stromal cells, macrophages, active oxygen species, cytokines, gamma radiation, mesenchymal cells, macrophages, reactive chemicals, cytokines

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