INVESTIGATION OF THE INFLUENCE OF THE CONDITIONING MEDIUM FACTORS OBTAINED DURING THE CULTIVATION OF BONE MARROW MESENCHYMAL STEM CELLS ON THE COURSE OF SEVERE LOCAL RADIATION INJURIES OF SKIN IN RATS
Abstract and keywords
Abstract (English):
Purpose: Study of the effect of paracrine factors, produced by MMSC of bone marrow during the cultivation, on the severity of local radiation injuries in the conditions of application in the early periods after irradiation. Material and methods: Experiments were performed on rats of the breed Wistar weighing 280 g. Rats were exposed locally in iliolumbar region of the back using X-ray machine LNC-268 (RAP 100-10) at a dose of 110 Gy (30 kV tube voltage, current 6.1 mA, filter Al 0.1 mm thick), dose rate is 21.4 Gy/min. Area of the irradiation field was 8.2–8.5 cm2. The conditioned medium obtained by culturing MMSC of rats’ bone marrow was administered in dose 1.0 ml (total protein 8 mg/ml) at 1, 3, 6, 8 and 10 days after irradiation. The severity of radiation damage to the skin and the effects of therapy were evaluated in dynamics by clinical manifestations, using planimetry and histological methods. Results: It was shown that in control animals and in rats, with the introduction of the conditioned medium, the values of the skin lesion area in the period up to the 29th day after irradiation practically did not differ, gradually decreasing in control animals from 5.9 ± 0.6 cm2 to 2.2 ± 0.3 cm2 at the 15th and 29th days after irradiation, respectively. Then, in the control group, the lesion area ranged from 1.4 ± 0.6 cm2 on the 50th day to 1.9 ± 0.8 cm2 on the 71st day. In the experimental group of animals, with the introduction of factors of the conditioning medium, a decrease in the area of the lesion and a stable dynamics of healing of radiation ulcers, beginning from the 36th day, there was a gradual decrease in the area of the lesion, which reached 0.2 ± 0.1 cm2 by the 71st day after irradiation. On the 64–71th day after irradiation, the difference between the areas of skin lesion in the experimental and control groups was statistically significant, p <0.05. The histological analysis showed that the use of paracrine factors obtained from MMSC in the process of cultivation significantly reduces the severity of the inflammatory reaction and accelerates the regeneration processes. Conclusion: Thus, the introduction of conditioned medium factors obtained during the cultivation of mesenchymal stem cells of the bone marrow facilitates a more easy flow of the pathological process and the healing of radiation ulcers after local radiation damage to the skin of rats. Apparently, the favorable effect of paracrine factors introduced in the early periods after irradiation, with severe local radiation injuries, is associated with their effect on pathological processes in the inflammatory-destructive stage.

Keywords:
paracrine factors, conditioned medium, cell technology, local radiation injuries, mesenchymal stem cells, bone marrow, radiation skin ulcers, rats
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Исследования на животных с целью изучения физиологических состояний и патологий у человека, согласно [1, 2], известны еще с V в. до н.э.; с тех пор в этом плане использовались сотни различных видов [2]. Первым животным объектом для систематических работ, судя по источнику [3], являлись крысы, применение которых в собственно научных целях известно еще с 16 в., но весьма многие изыскания проводились и на других специально разводимых животных, в частности, еще с 18 в. [4] на мышах [2, 4]. В настоящий период (2010 г. [4] и 2013 г. [3]) именно мыши и крысы выступают как основные лабораторные живот- ные, составляя 59 % [4] и 18–20 % [3–5] соответственно от общего числа млекопитающих, используемых в эксперименте1. (В российском руководстве от 2010 г. [6] приведена подробная история становления лабораторного животноводства в СССР, включая соответствующие правительственные документы.)

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