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Andrey Temnov,1–3 Tatyana Astrelina,1–3 Konstantin Rogov,1–3 Boris Moroz,1–3 Vladimir Lebedev,1–3 Tamara Nasonova,1–3 Alla Lyrshchikova,1–3 Olga Dobrynina,1–3 Yury Deshevoy,1–3 Alexander Melerzanov,3 Augustinus Bader,4 Apurva Mishra,3 Shibashish Giri,4,5 Valeriy Boyarintsev,1–3 Alexander Trofimenko,1–3 Andrey Bushmanov,1–3 Alexander Samoylov1–3 1State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow, Russia; 2Research Institute of Human Morphology, Russian Academy of Medical Science, Moscow, Russia; 3Faculty of Biological and Medical Physics. Moscow Institute of Physics and Technology (MIPT), Moscow Region, Russia; 4Applied Stem Cell Biology and Cell Technology, Biomedical and Biotechnological Center, Leipzig University, Leipzig, Germany; 5Department of Plastic and Hand Surgery, University Hospital Rechts der Isar, Munich Technical University, Munich, Germany Background: Mesenchymal stem cells based paracrine bioactive factors that deploy their task as an essential mechanism, but their efficiency for skin regeneration still requires clarification. Methods: The 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.Results: The 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. Conclusion: In 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. Keywords: Mesenchymal stem cells, MSC-based paracrine factors, radiation burn, skin regeneration