PROLONGATION OF CLEANSING DAMAGED TISSUES FROM DETRITUS USING EXOSOMES OF MULTIPOTENT STROMAL CELLS
Authors:   Federal Research Center of Fundamental and Translational Medicine of the Ministry of Science and Higher Education of the Russian Federation, Institute of Molecular Pathology and Pathomorphology, Maiborodin I.V. ,   Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch, Shevela A.A. ,   Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch, Marchukov S.V. ,   Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch, Morozov V.V. ,   Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch, Matveeva V.A. ,   Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch, Maiborodina V.I. ,   Federal Research Center of Fundamental and Translational Medicine of the Ministry of Science and Higher Education of the Russian Federation, Institute of Molecular Pathology and Pathomorphology, Novikov A.M. ,   Research Institute of Clinical and Experimental Lymphology, Tornuev Yu.V. ,   Federal Research Center of Fundamental and Translational Medicine of the Ministry of Science and Higher Education of the Russian Federation, Institute of Molecular Pathology and Pathomorphology, Churin B.V. ,   Federal Research Center of Fundamental and Translational Medicine of the Ministry of Science and Higher Education of the Russian Federation, Institute of Molecular Pathology and Pathomorphology, Shevela A.I. ,   Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch
Published: September 2021

Objective. To study the effect of exosomes of multipotent mesenchymal stromal cells (EMSCs) on soft tissues damaged during implantation of a metal screw into the bone. Methods. A defect (2 mm in diameter and 4 mm in depth) was created in the tibial proximal condyles of outbred rabbits. Metal screws were implanted into the defect by preliminary injection of saline (control, n=9 animals) or 19.2 μg of EMSCs per limb (experiment, n=10 rabbits). After 3, 7 and 10 days following the operation, the animals were taken out from the experiment; histological sections of soft tissues from the condyle surface, stained by hematoxylin and eosin were studied using light microscopy. Results. The use of water cooling in the process of introducing the metal implant into the tibial proximal condyle does not lead to complete removal of small bone fragments, which are subsequently either eliminated outward with wound discharge, or are destroyed and are subjected to lysis by macrophages. As a result of the EMSC effect on soft tissues near the site of damage, the activity of the postoperative inflammation reduces, leads to a slowdown in the resorption of hemorrhages, the elimination of fibrin clots, detritus and small bone fragments. Even on the 10<sup>th</sup> day after using EMSCs in the postoperative wound a structureless detritus with a small number of infiltrating cells was present, as well as a significant number of multinucleated macrophages with fused cytoplasm, non-viable lysed striated muscle symplasts and bone fragments with a low degree of degradation. Conclusion. Suppression of inflammation by EMSCs delays the clearance of the postoperative wound, promotes the prolongation of the repair process and the attachment of the granulomatous component to the inflammation. The using EMSCs in the process of intraosseous implantation may be recommended only to control the activity of the inflammatory process and only after maximum preliminary cleansing of the postoperative wound from detritus, including non-viable muscle tissue and bone fragments. What this paper adds It has been firstly shown that after the experimental use of exosome of multipotent mesenchymal stromal cells to influence the regeneration of surgical trauma of soft tissues after intraosseous implantation, it is possible to reduce the activity of the inflammatory reaction, which leads to a slowdown of resorption of hemorrhages, elimination of fibrin clots, detritus and small bone fragments and, accordingly, prolongation of cleansing damaged tissue and delayed repair.