JOURNAL DESCRIPTION
The Medical Radiology and Radiation Safety journal ISSN 1024-6177 was founded in January 1956 (before December 30, 1993 it was entitled Medical Radiology, ISSN 0025-8334). In 2018, the journal received Online ISSN: 2618-9615 and was registered as an electronic online publication in Roskomnadzor on March 29, 2018. It publishes original research articles which cover questions of radiobiology, radiation medicine, radiation safety, radiation therapy, nuclear medicine and scientific reviews. In general the journal has more than 30 headings and it is of interest for specialists working in thefields of medicine¸ radiation biology, epidemiology, medical physics and technology. Since July 01, 2008 the journal has been published by State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency. The founder from 1956 to the present time is the Ministry of Health of the Russian Federation, and from 2008 to the present time is the Federal Medical Biological Agency.
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Medical Radiology and Radiation Safety. 2020. Vol. 65. No. 1. P. 5–12
V.A. Brunchukov, T.A. Astrelina, V.A. Nikitina, I.V. Kobzeva, Yu.B. Suchkova, D.Yu. Usupzhanova, A.A. Rastorgueva, T.V. Karaseva, T.V. Gordeev, O.A. Maxsimova, L.A. Naumova, S.V. Lischuk, E.A. Dubova, K.A. Pavlov, V.A. Brumberg, A.E. Makhova, E.E. Lomonosova, E.I. Dobrovolsskaya, I.M. Barabash, A.Yu. Bushmanov, A.S. Samoilov
Experimental Treatment of Radiation Skin Lesions with Mesenchymal Stem Cells and Their Conditioned Media
A.I. Burnasyan Federal Medical Biophysical Center, Moscow, Russia
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Abstract
Purpose: To study the regeneration processes in the treatment of radiation skin lesions with the mesenchymal stem cells (MSC) derived from human gingiva and their conditional medium concentrate (CCM) during animal studies.
Material and methods: The study includes 80 white male Wistar rats weighing 210 ± 30 g at the age of 8–12 weeks, randomized into 4 groups (20 animals in each): control group (C), animal did not receive treatment; control with the introduction of the conditional medium concentrate (CCM) three times on days 1, 14 and 21; the introduction of MSC in a dose of 2 million cells per 1 kg three times on days 1, 14 and 21; the introduction of CCM in the estimated dose of 2 million cells per 1 kg three times on days 1, 14 and 21. Radiation burn simulation was performed (using on an X-ray unit at a dose of 110 Gy) and each animal was observed 17 times: at days 1, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, 91, 98, 105 and 112. Histological (stained with hematoxylin-eosin) and immunohistochemical (CD31, CD68, and VEGF) studies were performed. MSC was cultivated according to the standard procedure up to passages 3–5, the conditioned medium was collected and concentrated 10 times. The MSC immunophenotype (CD34, CD45, CD90, CD105, CD73, HLA-DR) and viability (7-ADD) were determined using flow cytometry.
Results: Under the assessment of the animal skin on the day 7 in the CCM group, the area was significantly larger compared to the C, MSC, CM groups (р ≤ 0.05). In the CM group on the day 14 the area of the open wound surface and ulcers from day 28 to day 42 was significantly less, compared with the C, MSC and CCM groups (р ≤ 0.05). In group C, from 42 to 77 days of observation, an increase in the area of skin ulcers was observed compared with the CM and CCM groups (р ≤ 0.05). On the day 112, healing of skin ulcers in the CM group was observed in 40 %, in the MSC group in 60 %, and only in 20 % of animals in the CCM group, and in the C group it was not registered. Expression of VEGF marker on endothelial cells and stromal cells was observed in groups C and CM on day 28 and in groups MSCs and CCM on day 112. On the 28th day in the MSC group, the average number of vessels (CD31) in the field of view was 6.0, and on day 112 it was 12.75, р ≤ 0.05, in the CCM group – 19.10 and 28.6, respectively, р ≤ 0.05. An increase in the number of macrophages (CD68) was found in group C from 28 to 112 days (11.6 and 24.73, р ≤ 0.05), and in the CM group the decrease was 22.1 and 13.07, respectively, р ≤ 0.05.
Conclusion: Thus, all used treatment modes of radiation skin lesions, including 3-fold administration of CM, MSC and CCM at a dose of 2 million cells per 1 kg, were effective and resulted in a reduction in the damage area, accelerated ulcer healing, and improvement of the regenerative processes. In addition, the use of MSCs led to the improvement of inflammatory processes’ vascularization and reduction in the radiation skin lesions.
Key words: mesenchymal stem cells, radiation skin lesions, conditioned medium, cellular technologies, X-rays, skin
For citation: Brunchukov VA, Astrelina TA, Nikitina VA, Kobzeva IV, Suchkova YuB, Usupzhanova DYu, Rastorgueva AA, Karaseva TV, Gordeev TV, Maxsimova OA, Naumova LA, Lischuk SV, Dubova EA, Pavlov KA, Brumberg VA, Makhova AE, Lomonosova EE, Dobrovolsskaya EI, Barabash IM, Bushmanov AYu, Samoilov AS. Experimental Treatment of Radiation Skin Lesions with Mesenchymal Stem Cells and Their Conditioned Media. Medical Radiology and Radiation Safety. 2020;65(1):5-0. (In Russ.).
DOI: 10.12737/1024-6177-2020-65-1-5-12
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PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The study was financially supported by the Federal Target Program “Ensuring Nuclear and Radiation Safety for 2016–2020. and for the period until 2030”. A series of publications is planned based on the results of the studies.
Contribution: Article was prepared with equal participation of the authors.
Compliance with the rules of bioethics. The study was performed in accordance with the ethical standards for the treatment of animals adopted by the European Convention for the protection of vertebrates used for research and other scientific purposes.
Article received: 12.10.2018. Accepted for publication: 11.12.2019