PROTECTION OF NEURAL STEM CELLS FROM GENOTOXIC EFFECTS BY FACTORS SECRETED BY MESENCHYMAL STEM CELLS

DOI: https://doi.org/10.29296/24999490-2018-06-05

G.A. Posypanova(1), M.G. Ratushnyak(1, 2), O.V. Vysotskaya(1), A.I. Glukhov(2), Yu.P. Semochkina(1), A.V. Rodina(1, 2), E.Yu. Moskaleva(1, 2) 1-National Research Centre «Kurchatov Institute», Akademika Kurchatova pl., 1, Moscow, 123182, Russian Federation; 2-I.M. Sechenov First Moscow State Medical University, Trubetskaya str., 8–2, Moscow, 119991, Russian Federation E-mail: [email protected]

Introduction. The brain injury induced during radiotherapy and chemotherapy is largely dependent on a disruption of neurogenesis in the subgranular zone of the dentate gyrus in the hippocampus as a result of the neural stem cells (NSCs) damage. The aim of the study. The purpose of this work was to characterize the protective potential of mesenchymal stem cells (MSCs) isolated from different mouse tissues, on the level of gene expression and activity of neurotrophins and on the secretion of a number of cytokines, and to study the possibility of the increasing in the survival of mouse NSCs after irradiation and after the action of etoposide, an antitumor drug that causes DNA damage. Results. A high sensitivity of the mouse NSCs to the action of γ-radiation and etoposide is shown. When comparing MSCs from bone marrow, brain and adipose tissue, the highest level of neurotrophin genes NGF, BDNF, NT4 and GDNF expression is found in MSCs from the adipose tissue. The high activity of neurotrophins, high concentration of IL6, HGF, TGFβ and VEGF and the absence of G-CSF, bFGF and IL10 cytokines were detected in the culture medium conditioned with MSC from the adipose tissue. An increase in the survival of NSCs was observed when NSCs were cultured in the presence of conditioned medium from mouse adipose tissue-derived MSCs, both after the gamma-irradiation and after the action of etoposide. Conclusion. The results explain the protective effect of MSCs in radiation injuries and for the first time demonstrate an increase in the NSCs survival after irradiation and the action of etoposide due to the influence of secreted MSCs factors.
Keywords: 
neural stem cells, radiosensitivity, etoposide, mesenchymal stem cells, neurotrophins, cytokines, cell therapy, mouse
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