**4. Discussion**

Skin LRIs pose a serious medical, social, and economic problem. It is known that early effects of skin damage from ionizing radiation (dry and wet dermatitis) are associated with damage to the epidermis, and late effects (skin atrophy, radiation necrosis, etc.) are the result of damage to the dermis [4]. Thus, the radiation target of the epidermis is the highly radiosensitive cells of the basal layer, and the vessels of the microcirculatory bed in the dermis. As a result, with deep radiation burns, necrotic and degenerative processes cover all layers of the skin, gradually spreading to the underlying tissues, up to the bone.

This study is aimed at preventing complications of late radiation injuries, improving the nature of the treatment course, and speeding up the healing time of skin LRIs. The introduction of MSCs, culture, and conditioned media was performed three times: in the absence of changes in the skin (day 1), after the formation of radiation dermatitis (day 14), and after the appearance of the wound surface (day 21) to activate reparative processes and angiogenesis in damaged skin, reduce the healing time of ulcerative defects, and prevent relapses.

In the course of the present study, the use of a conditioned medium concentrate and culture medium showed greater effectiveness in terms of reducing the time and area of the open wound surface. The greatest number of cases of complete healing of the affected skin of animals by the end of the observation period (112 days) was detected in the CMPL group, and healing was also noted in the CM group. In the same groups, no clinical signs of LRI recurrence were detected, but not in the C and PL groups (Figure 3).

In our previous study [7], the effectiveness of the use of MSCs of the gingival mucosa in LRI was shown. The absence of a significant effect when using MSCs derived from the placenta in this study is due to the tissue specificity of this cell source and the peculiarities of their production of paracrine factors.

According to the histological study, there was a decrease in inflammatory processes, the presence of hair follicle rudiments, and proliferation of microcirculatory vessels in the CMPL group, in contrast to other groups in which these changes were not so noticeable.

Given the nature of the radiation damage in all groups, the regenerative potential of cells in the affected area is significantly reduced, which was confirmed by data from immunohistochemical research. An increase in the expression of metalloproteinases (MMP 2 and 9), TIMP 2, collagen I and III, as well as the number of CD68 macrophages, was observed in the CMPL group on day 112, which probably indicates an increase in the rate of scarring and healing of the wound surface, which is confirmed by planimetric studies (Figure 4a,b).
