Pathomorphological and immunophenotypic evaluation of the efficacy and safety of different methods of exosome application in vivo

Background. Exosomes are membrane vesicles that carry the function of intercellular communication, they affect the proliferation and differentiation of cells, apoptosis, angiogenesis, immune response. These properties make exosomes attractive for the development of therapeutic strategies in dermatology and aesthetic medicine. There are ongoing discussions about a potential link between exosome application and effects such as carcinogenesis, autoimmunization, and impaired fibroblast migration, although the evidence remains controversial. It has been proposed that exosomes can be utilized at the skin surface without reaching the underlying tissue. Objective. To evaluate the carcinogenic potential, immunogenic properties, ability to affect the dermal cells of the exosome preparation from mesenchymal stem cells of human adipose tissue and plant-derived extracellular vesicles under the conditions of experimental model. Material and methods. An experimental model of cicatricial skin changes was reproduced on Wistar rats (n=16). Animals in the 1st group received exosomes topically after exposure to dermaroller, in the 2nd group — subcutaneously, in the 3rd group animals received 0.9% saline solution after dermaroller application, in the 4th group animals were not treated. Animals were removed from the experiment, skin fragments were subjected to histological and immunohistochemical analyses. Computer morphometry and statistical processing of the results were performed. Results. Histological study has revealed reduced collagen fragmentation and a large number of capillaries in samples of the 1st and 2nd groups. Immunohistochemical analysis has shown an enhancement of the synthesis of type III collagen in these groups compared to the control groups, absence of increase in the expression of Ki67 and mTOR markers. The samples treated with exosomes have shown a predominance of M2 macrophages compared to the control groups, levels of anti-inflammatory cells in all groups were comparable. The method of application has not significantly affected the efficacy and safety. Conclusion. The performed study did not provide convincing data on carcinogenic or anti-inflammatory effects of exosomes, as well as on their negative effect on fibroblast migration, but showed a significant enhancement of the process of controlled remodeling of the fibrous connective tissue matrix.