Morphology of the Myocardium after Experimental Bone Tissue Trauma and the Use of Extracellular Vesicles Derived from Mesenchymal Multipotent Stromal Cells.

Abstract

The effect of extracellular vesicles (EVs) of various origins on the heart structures in the time of health and disease has been well studied. At the same time, data on the distribution of EVs throughout the body after introduction into the tissues and the possibility of the influence of these EVs on organs distant from the injection site are practically absent. It is also necessary to note a certain inconsistency in the results of various researchers: from articles on the direct absorption of EVs derived from mesenchymal multipotent stromal cells (MSC EVs) by cardiomyocytes to the data that the heart is inherently immune to drug delivery mediated by nanoparticles. In this regard, the morphological changes in the myocardium of outbred rabbits of both sexes weighing 3–4 kg were studied at various times after experimental trauma of the bone tissue in the proximal condyle of the tibia (PCT) and the use of MSC EVs. As a result of modeling the PCT defect, rabbits develop myocardial edema in the heart muscle by the 3rd day, their lymphatic vessels expand, and then, on the 7th day, the blood vessels become dilated. In the myocardium, the relative and absolute contents of neutrophils, erythrocytes, and macrophages increase, but the percentage of lymphocytes decreases. By day 10, almost all of these changes return to their initial values. The detected transformations of the myocardium are most likely due to the ingress of detritus with the blood flow from the PCT. The use of MSC EVs to influence the regeneration of damaged tissue of PCT promotes earlier dilatation of the blood vessels of the heart with pronounced diapedesis of erythrocytes or even hemorrhages, prolongation of edema, the formation of blood clots in vessels with obliteration of their lumen, sclerotic transformation of vascular walls and paravascular tissues. In the myocardium, the number density of neutrophils, the percentage of lymphocytes, and neutrophils become smaller, with a simultaneous increase in the relative numbers of erythrocytes and macrophages, and changes in the content of macrophages remained until the end of the observation—up to 10 days after the surgery. The discovered effect of MSC EVs is most likely associated with the suppression of the activity of the inflammatory process in the PCT area, which, in turn, was caused by a longer ingress of detritus with blood flow into the myocardium. The absence of statistically significant differences between changes in the myocardium of the left and right ventricles may indicate that both detritus from the surgical site and MSC EVs affect the heart spreading through the coronary artery system.