Transplantation of mesenchymal stem cells (MSCs), at early and later stages after local exposure of rats to 140 Gy 90Sr/90Y beta radiation, was found to stimulate recovery of damaged skin. The area of local radiation injuries (LRIs) and accelerated healing of radiation ulcers was obtained. Clinical evolution showed the high efficiency of the transplantations of autologous MSCs for the treatment of deep beam ulcers, usually refractive to standard conservative treatment. Analogous to our results in the rats the authors obtained promising results with the application of MSCs for the treatment of severe LRIs in two human patients. Their radiation ulcers showed complete healing after stem cell application. Thus, further developments should determine the best possible conditions for MSC use in LRI treatment.

BackgroundMesenchymal stem cells based paracrine bioactive factors that deploy their task as an essential mechanism, but their efficiency for skin regeneration still requires clarification.MethodsThe mesenchymal stem cell-based paracrine factors were administered by subcutaneous injection of 0.5 mL peptides (general protein 8 mg/mL). These were performed after radiation on different days like the first, third, sixth, eighth, and 10th. To determine the consequences, we performed photography, planimetry, and preclinical test each week after 15 days of radiation. MSC-based peptides were injected into a rat that had radiation burns, and its observation encouraged cell-free therapeutic remedies to regenerate skin. Both control and experimental groups were exposed to 110 Gy of X-rays, which resulted in the formation of localized radiation burns on the skin (S=6 cm2) 15 days later. Thirty days after radiation, the wound stabilized (surface of the wound was S=2.2±0.2 cm2) and fluctuated throughout the course of the pathological process.ResultsThe wounded area on the skin from the 15th to the 29th day after radiation was practically the same in both groups. The wounded area gradually reduced by 6.1±0.4 cm2 (experimental group) and 5.9±0.6 cm2 (control group) 15 days after radiation up to 2.2±0.3 cm2 (in both control and experimental groups) on the 29th day after radiation. However, starting from the 36th day, there was a constant reduction in the burn area in the experimental group up to 0.2±0.1 cm2 till the 71st day after radiation.ConclusionIn the control group, the area of the lesion ranged from 1.4±0.6 cm2 on the 50th day to 1.9±0.8 cm2 on the 71st day. During the 57th to the 71st day, the difference between the affected area in the experimental and control groups was 1:8. The experimental group has a significantly higher level of skin regeneration and significant decrease in the level of leukocyte infiltration, thereby reducing necrosis.

Местные лучевые поражения (МЛП) в форме лучевых язв, сформированные в результате локального воздействия источников ионизирующего излучения, характеризуются длительным волнообразным течением, плохим прогнозом в отношении самостоятельного заживления и требуют специализированных высокотехнологичных способов лечения. Одним из компонентов их патоморфогенеза является поражение сосудов микроциркуляторного русла, что наряду с повреждением клеток эпителиальной и соединительной тканей служит одной из причин морфологических особенностей развития этого вида повреждения. Генная индукция роста сосудов микроциркуляторного русла может стать одним из компонентов местного лечения МЛП.Цель исследования -оценить влияние проангиогенного геннотерапевтического препарата на основе pl-vegf165 («Неоваскулген», Россия) на процессы заживления в экспериментальной модели длительно незаживающих тяжелых местных лучевых поражений (язв).Материал и методы. Эксперимент проведен на белых крысах-самцах (n=40), которые были разделены на 4 группы по 10 животных: контроль, группа с однократным введением препарата через 14 сут после облучения, группа с двукратным введением через 14 и 27 сут, и группа с однократным поздним введением -через 35 сут. Основным критерием оценки заживления была макроскопическая планиметрия. Выполнены рутинные гистологическое и морфометрическое исследования.Результаты. Установлено, что статистически значимые различия динамики заживления МЛП по критерию площади язвенной поверхности получены между группами контроля и экспериментальными группами в отдаленный период -при наблюдении более чем через 60 сут.Заключение. Выявленный результат может быть объяснен динамикой развития новых сосудов микроциркуляторного русла, образовавшихся в результате генной индукции ангиогенеза.Ключевые слова: местные лучевые поражения, лучевая язва, генная терапия, эндотелиальный сосудистый фактор роста, vegf165.

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.