Multipotent mesenchymal stem cells (MMSCs) are known to be excellent therapeutic agents. Apart from their ability to differentiate into various cell types, and thus participate in the repair of injured tissues and organs, they can influence the regeneration process through secretion of paracrine factors. Thus, MMSC therapy represents a special type of medical intervention that has both a systemic range of therapeutic efficacy and local activity on individual sites of an organ. Over the past decades, MMSC therapy has continuously been in a cautious transition from research development to clinically approved therapies. Clinical trial data has shown that this therapy is rarely associated with severe adverse events, is well tolerated and quite safe in the short-term period. However, it has a number of limitations for use, mainly due to the risk of malignant transformation. The success of stem cell transplantation in the treatment of various diseases has been confirmed both in preclinical studies and in clinical practice. The main issues that arise when assessing the therapeutic efficacy of MMSC-associated therapy are the type of cells (adipogenic, bone marrow, etc.), delivery route, number of cells injected, and the optimal number of injections. There is a growing body of experimental and clinical evidence suggesting that both an adequate delivery route and an adequate dose can increase the likelihood of success of MMSC-associated. Each cell delivery route has costs and benefits. However, there is generally contradictory evidence on the comparative efficacy of different cell delivery routes. The optimal dose of transplanted cells is also debated, as high MMSC doses may increase the risks of complications and may not have the proper effect both when administered systemically and locally. These aspects require further systematization of available data to maximize the effect of cell therapy by selecting the safest and most appropriate approaches.

The radioprotective efficacy of recombinant flagellin (FL) and interleukin-1 beta (IL-1) administered in combinations for preventive or therapeutic purposes was studied in experiments on white mongrel mice. The drugs were administered i.p. at doses of 1 mg/kg (FL) and 50 μg/kg (IL-1β). Simultaneous administration of the drugs in the early stages before irradiation was shown to be most efficacious in terms of 30-day survival of mice exposed to x-rays at a dose of 7.5 Gy (100% survival of mice vs. 53% survival in the control group, p < 0.01). Sequential administration of FL before exposure and IL-1β after exposure increased survival of the mice by 40% ( p < 0.05). The results indicated that combined use of biotechnological drugs for radioprotection was promising.

Research objective. To evaluate the radioprotective effectiveness of recombinant flagellin when used alone or in combination with interleukin-1 beta for prophylactic or therapeutic effect on animals. Materials and methods. The effect of hybrid flagellin FliC Salmonella typhimurium and human interleukin-1β (Institute of Highly Pure Biopreparations, Saint Petersburg, Russia) on the 30-day survival of male mice exposed to lethal doses of X-ray radiation was studied. Survival of irradiated animals was analyzed by Kaplan-Meier method. Results. The preventive use of flagellin had a protective effect on the 30-day survival of mice irradiated with lethal doses of X-rays. Compared with the irradiated control, the administration of flagellin (1 mg/kg or 2 mg/kg) prior to X-ray exposure (7.5 Gy, 8.0 Gy or 8.5 Gy) increased the animal survival rate to 67-87%. Complex preventive administration of flagellin (1 mg/kg) and interleukin-1 beta (50 μg/kg) provided a 100% survival rate of the irradiated mice. Separate use of drugs was also effective; 92.8% of mice survived when flagellin was administered prior to irradiation and interleukin after. Conclusion. Recombinant flagellin is a promising candidate product for designing new generation of domestic radiation countermeasures, including combinations with interleukin-1 beta.

The estimation of efficiency of consecutive application of radioprotector B-190 and interleukin-1beta administered at early times after acute irradiation by studying the changes of the number of peripheral blood leukocytes, neutrophils and lymphocytes, as well as cytochemical research into the contents of glycogen, myeloperoxidase and alkaline phosphatase in neutrophils of the irradiated mice was carried out. It is established that administration of radioprotector B-190 at a doze of 50 mg/kg for 15 minutes before irradiation and interleukin-1beta at a doze of 50 mkg/kg for 15 minutes after irradiation reduces the expressiveness of post-irradiation leukopenia, accelerates restoration of the number of neutrophils and lymphocytes in peripheral blood, normalizes the functional status of neutrophils of irradiated mice to a greater degree than their isolated introduction.

The study was aimed at evaluating the radioprotective effectiveness of genistein administered at different times before or after acute irradiation. Evaluation ofradioprotective efficiency was performed by studying the 30-day survival rate, life expectancy, bone marrow hemapoiesis using the method of endogenous and exogenous colony formation. We have established that genistein at a dose of 200 mg/kg when administered 1 hour prior to irradiation has the highest radioprotective efficiency. In this case, genistein protects mice against death due to X-ray radiation at doses LD(50-90/30), increasing their survival rate by 30-44%, and reduces expression of post radiation disorders of bone marrow hematopoiesis.

Проведена оценка радиозащитной эффективности отечественного синтетического препарата генистеина при его введении в разные сроки до или после радиационного воздействия путем изучения 30-суточной выживаемости, средней продолжительности жизни погибших животных, исследования костномозгового кроветворения облученных мышей в методике эндо- и экзогенного колониеобразования. Установлено, что генистеин в дозе 200 мг/кг при введении за 1 ч до облучения обладает наибольшей радиозащитной эффективностью. При этом он снижает постлучевую гибель мышей, подвергнутых рентгеновскому облучению в дозах СД50-90/30, увеличивая их выживаемость на 30–44%, а также уменьшает выраженность постлучевых нарушений костномозгового кроветворения.

The study was aimed at evaluating the radioprotective effectiveness of beta-estradiol following its prophylactic administration in conditions of acute irradiation. Evaluation of the radioprotective efficiency was performed by studying the 30-day survival rate, life expectancy, the structure of irradiated mice death, the bone marrow hematopoiesis using the method of exogenous colony formation. The prophylactic use of beta-estradiol at doses of 20 and 40 mg/kg 5 days before irradiation has been established to protect the exposed mice against radiation death induced by X-rays at doses LD50-90/30, thus increasing their survival rate by 17-58%, and to favor the reduced expression of post radiation disorders of bone marrow hematopoiesis.

The purpose of the study is evaluation of radioprotective effectiveness of indometofen at its prophylactic administration in conditions of acute irradiation. Evaluation of radioprotective efficiency was performed by studying the 30-day survival rate, life expectancy, structure of deathly irradiated mice, and bone marrow hemopoiesis using methods of endogenous and exogenous colony formation. The prophylactic application of indometofen at doses 30 mg/kg for 5 days before irradiation has been observed to protect mice against radiation death induced by gamma or X-ray exposures at doses LD(50-70/30), increasing their survival rate by 16-44%, and reduce severity of post radiation disorders of bone marrow hemopoiesis.

Цель исследования – экспериментальная оценка эффективности последовательного применения радиопротектора препарата Б-190 и средства экстренной терапии радиационных поражений интерлейкина-1? при остром облучении. Оценку лечебно-профилактического действия данной схемы введения препаратов проводили путем изучения 30-суточной выживаемости и средней продолжительности жизни погибших животных, исследования костномозгового кроветворения в методиках эндогенного и экзогенного колониеобразования. Установлено, что последовательное применение препарата Б-190 в дозе 50 мг/кг за 15 мин до облучения и интерлейкина-1? в дозе 50 мкг/кг через 15 мин после радиационного воздействия увеличивает выживаемость и предотвращает постлучевое снижение количества КОЕ-С9 у облученных мышей в большей степени, чем их изолированное введение.

The purpose of research was the experimental estimation of efficiency of consecutive application of a radioprotector B-190 and means of emergency therapy of radiating injury interleukin-1beta at acute irradiation. An estimation of treatment-and-prophylactic action of the given circuit of introduction of preparations carried out by studying 30 day-survival and average life expectancy of the lost animals, research of bone marrow hemopoiesis. It is established, that consecutive application of a radioprotector B-190 in a doze of 50 mg/kg for 15 mines up to an irradiation and interleukin-1beta in a doze of 50 mkg/kg through 15 mines after irradiating increases survival and prevents decrease in quantity of CFU-S9 at the irradiated mice in the greater degree, than their isolated introduction.