Malignant Transformation of Mesenchymal Stem Cells from Different Mouse Tissues  after Mixed Gamma-Neutron Irradiation in vitro

Yu. P. Semochkina; A. Rodina; E. Y. Moskaleva; E. Zhorova; V. Saprykin; S. Arzumanov; V. Safronov

doi:10.12737/article_5c55fb17a02054.31513592

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MALIGNANT TRANSFORMATION OF MESENCHYMAL STEM CELLS FROM DIFFERENT MOUSE TISSUES AFTER MIXED GAMMA-NEUTRON IRRADIATION IN VITRO Malignant Transformation of Mesenchymal Stem Cells from Different Mouse Tissues after Mixed Gamma-Neutron Irradiation in vitro

АА Аа

Published in Medical Radiology and radiation safety · Volume 64, Issue 1 · Pages 5–14 · Rubric: Radiation biology

DOI: https://doi.org/10.12737/article_5c55fb17a02054.31513592

Received: 20.01.2019 Accepted: 24.03.2024 Language of publication: RUS

Authors

Yu. P. Semochkina

A. Rodina

E. Y. Moskaleva

E. Zhorova

et al.

V. Saprykin

S. Arzumanov

V. Safronov

Yu. P. Semochkina

NRC Kurchatov Institute Junior Researcher · Russian Federation · Moscow

A. Rodina

Academic degree: candidate of sciences in biology

NRC «Kurchatov Institute» Leading Researcher · Russian Federation · Moscow

E. Y. Moskaleva

Academic degree: doctor of sciences in biology

Science rang: professor

NRC «Kurchatov Institute» Leading Researcher · Russian Federation · Moscow

E. Zhorova

Academic degree: candidate of sciences in biology

A.I. Burnasyan Federal Medical Biophysical Center of FMBA Leading Researcher · Russian Federation · Moscow

V. Saprykin

Academic degree: doctor of medical sciences

A.I. Burnasyan Federal Medical Biophysical Center of FMBA Leading Researcher · Russian Federation · Moscow

S. Arzumanov

Academic degree: candidate of physical and mathematical sciences

NRC «Kurchatov Institute» Deputy Head of Department · Russian Federation · Moscow

V. Safronov

Academic degree: candidate of physical and mathematical sciences

Research Center “Space Materials Science” Senior Researcher · Russian Federation · Kaluga

ABSTRACT

Purpose: To study the possibility of malignant transformation of control and irradiated mesenchymal stromal stem cells (MSC) from the bone marrow (BM) and brain (BR) and from the adipose tissue (AT) of mice and some cytokines secretion after mixed γ,neutron (γ, n) irradiation and γ-irradiation. Material and methods: MSCs were isolated and cultured according to generally accepted protocols. γ, n-irradiation was carried out by a collimated beam of neutrons and gamma rays at a special station of the nuclear reactor IR-8. MSCs were irradiated at the 29th passage at doses of 0.05; 0.5 and 2 Gy, were cultured for 10 passages and transplanted subcutaneously 1×106 cells to C57BL/6 syngeneic mice. MSCs AT were irradiated at the facility GUT-200M (60Co) at doses 1–6 Gy. The level of cytokines in the culture medium of MSC was measured by an ELISA. Results: A decrease in RBE was observed after radiation dose increasing from 0.5 to 4.0 Gy. The maximum of RBE for all MSCs, equal to 5.5, was observed at a dose of 0.5 Gy. After the dose increasing to 2 Gy an average RBE decreased to 2.5, and at dose 4.0 Gy RBE it was 2.0. Tumors were detected after 5 months after transplantation into syngeneic mice of MSC BM irradiated at doses of 0.05; 0.5 and 2 Gy. After transplantation of control MSCs BM and of control and irradiated MSCs BR and MSC AT, no tumors were detected. After subcutaneous injection of γ-irradiated at doses of 0.1; 1 and 6 Gy MSC AT, unlike MSCs BM, no tumors were detected. Histological examination of tumors revealed signs of a low-grade fibrosarcoma with active proliferation and a high degree of malignancy. Tumors contained inclusions from the derivatives of several tissues of mesenchymal origin – muscular, fatty, cartilaginous and bone. In the case of a tumor that developed after transplantation of MSCs BM exposed to γ,n-radiation at a dose of 0.05 Gy, the contact metastasis was detected in the shoulder with the penetration of tumor cells between the muscle fibers. From the tumors, the mouse fibrosarcoma cell lines were obtained. The highest level of cytokines VEGF, HGF and IL6was found in the culture medium of MSC AT. The level of TGFβ secretion was practically the same in all studied MSCs. After γ,n-irradiation an increase of VEGF secretion in MSC BM, a decrease of IL6 secretion in MSC BM and MSC BR, and an increase in its secretion in MSC AT were detected. Conclusions: The obtained results testify the high sensitivity of MSC BM to malignant transformation after ionizing irradiation and the much higher resistance of mouse MSC BR and MSC AT. The mechanisms of these differences are yet not known. The highest level of cytokines VEGF, HGF and IL6 was found in the culture medium of MSC AT. After the action of γ,n-radiation, as well as after the action of γ-radiation, the secretion profile of the investigated cytokines was changed, depending both on the dose and on the type of radiation.

KEYWORDS

mesenchymal stem cells, malignant transformation, carcinogenesis, γ-irradiation, γ, n-irradiation, neutrons, bone marrow, brain, adipose tissue, cytokines, mice

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GOST

Semochkina Y. P., Rodina A. V., Moskaleva E. Y., Zhorova E. S., Saprykin V. P., Arzumanov S. S., Safronov V. Malignant Transformation of Mesenchymal Stem Cells from Different Mouse Tissues after Mixed Gamma-Neutron Irradiation in vitro // Medical Radiology and radiation safety. 2019. no. 1. pp. 5-14. DOI: https://doi.org/10.12737/article_5c55fb17a02054.31513592. (Date of access 10.10.2026).

MLA

Yu. P. Semochkina, Rodina A. V., Moskaleva E. Y., Zhorova E. S., Saprykin V. P., Arzumanov S. S., Safronov V.. "Malignant Transformation of Mesenchymal Stem Cells from Different Mouse Tissues after Mixed Gamma-Neutron Irradiation in vitro." Medical Radiology and radiation safety 64.1 (2019): 5-14. DOI: https://doi.org/10.12737/article_5c55fb17a02054.31513592.

APA

Semochkina Y. P., Rodina A. V., Moskaleva E. Y., Zhorova E. S., Saprykin V. P., Arzumanov S. S., Safronov V. (2019). Malignant Transformation of Mesenchymal Stem Cells from Different Mouse Tissues after Mixed Gamma-Neutron Irradiation in vitro. Medical Radiology and radiation safety, 64(1), 5-14. https://doi.org/10.12737/article_5c55fb17a02054.31513592

Chicago

Yu. P. Semochkina, Rodina A. V., Moskaleva E. Y., Zhorova E. S., Saprykin V. P., Arzumanov S. S., Safronov V.. "Malignant Transformation of Mesenchymal Stem Cells from Different Mouse Tissues after Mixed Gamma-Neutron Irradiation in vitro." Medical Radiology and radiation safety 64, no. 1 (2019): 5-14. https://doi.org/10.12737/article_5c55fb17a02054.31513592.

WIKI

{{cite journal | author = Semochkina Y. P., Rodina A. V., Moskaleva E. Y., Zhorova E. S., Saprykin V. P., Arzumanov S. S., Safronov V. | title = Malignant Transformation of Mesenchymal Stem Cells from Different Mouse Tissues after Mixed Gamma-Neutron Irradiation in vitro | journal = Medical Radiology and radiation safety | year = 2019 | volume = 64 | issue = 1 | pages = 5-14 | doi = 10.12737/article_5c55fb17a02054.31513592 }}

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MALIGNANT TRANSFORMATION OF MESENCHYMAL STEM CELLS FROM DIFFERENT MOUSE TISSUES AFTER MIXED GAMMA-NEUTRON IRRADIATION IN VITRO Malignant Transformation of Mesenchymal Stem Cells from Different Mouse Tissues after Mixed Gamma-Neutron Irradiation in vitro

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