**1. Introduction**

Today, ionizing radiation sources are widely used in various fields of human activity, and their scope is constantly expanding, which increases the risk of radiation damage [1,2]. Studies have shown that radiation damage to the skin causes damage to the stem and proliferating cells of the epidermis, as well as in the vessels of the microcirculatory bed [3–5], so the final effect of ionizing radiation is determined by the balance between damage to the cells and recovery processes in the affected area and adjacent tissues [4,6].

Radiation to human skin in doses exceeding 8 Gy may lead to the development of local radiation injuries (LRI) [4]. In radiotherapy of oncological diseases, LRI is registered in 20–40% of cases [7]. Skin LRIs are characterized by the development of recurrent ulcers with pain syndrome, which significantly lengthens the treatment process due to persistent damage to blood and lymphatic vessels with the progression of tissue fibrosis, which worsens the results of treatment and the quality-of-life of patients [7]. Currently, there are no effective treatments for LRI.

Taking into account the pathogenetic mechanisms of radiation-induced lesions, the use of cellular technologies using mesenchymal stem cells (MSCs) and their waste products (paracrine factors) may become a promising method of treating skin LRI [5]. MSCs are capable of self-renewal and various types of differentiation in the adipogenic, osteogenic, chondrogenic, and myogenic directions [1]. The use of MSCs leads to the healing of the wound surface of the skin and its appendages, diabetic ulcers, damage to skeletal muscles and cartilage, and the heart. Intravenous, local administration of MSCs helps to reduce necrotic changes, reduce inflammation, and significantly improve the processes of granulation, reepithelialization, neoangiogenesis, and hair restoration [1,3,4].

The main effect of MSCs may be due to their secretory activity, associated with the production of a wide range of cytokines and growth and angiogenic factors [8]. Paracrine factors initiate the stimulation of host MSCs, triggering the regeneration of damaged tissues. Thus, the cytokines involved in the regulation of the inflammatory process include IL-1β, 4, 6, 10, 12, and 17, TNF-α, TGF-β1, PGE-2, PDGF, HGF and SDF-1. VEGF, FGF-2, EGF, TGF-α, HGF, IGF-1, etc., are responsible for neoangiogenesis, and the regulation of tissue fibrosis involves the participation of IL-4, 16, TGF-β1, HGF, bFGF, etc. MSC secretome injections in the form of conditioned media containing extracellular vesicles also have positive effects, as well as the MSCs themselves. Further assessment of the paracrine potential of MSCs may open up new ways of treating acute and chronic forms of MLP of the skin [1,3,4].

One of the most important advantages of MSCs is their low immunogenicity, which allows the use of allogeneic MSCs without the risk of rejection reactions. Sources of MSCs are various human tissues (bone marrow, adipose tissue, skin, placenta, synovial membrane, cartilage, etc.) [1,3,4,6,7]. The main sources of MSCs are bone marrow, mucosal and placental tissues, etc.

Placental tissue is of great interest due to the simplicity of sampling, the absence of ethical problems, and the ability to quickly obtain and accumulate the necessary amount of cellular material. MSCs derived from the placenta are known to have a higher regenerative potential compared to cells from other sources, but there are no data on the use of these cells in LRI [9].

Thus, the presented data indicate that MSCs derived from the placenta and the paracrine factors produced by them can be used to produce drugs intended for the treatment of LRI, which undoubtedly deserves further study.

The aim of this study was to study the effect of human MSCs derived from the placenta and their conditioned medium concentrate on skin regenerative processes in laboratory animals with LRI.
