Adult stem cells, such as MSCs, spontaneously differentiate in vitro. This makes it difficult both to study this important cell type and to grow large numbers of MSCs for clinical use. While conventional cell cultivation methods cannot cope with this problem, nanostructured materials science offers hope. The effect of small-sized spherical nanoparticles based on orthovanadates of rare-earth elements activated by europium (GdYVO4:Eu3+ nanoparticles, diameter 1–2 nm) on cell-cell adhesion of rat bone marrow mesenchymal stem cells (rBM-MSCs) in vitro was studied using electrophoretic separation of proteins, immunofluorescence and confocal laser scanning microscopy. Our study revealed that rBM-MSCs treated with small-sized GdYVO4:Eu3+ nanoparticles had a significant impairment of intercellular adhesion in vitro. The pre-incubation of mesenchymal stem cells of rat bone marrow with GdYVO4:Eu3+ nanocrystals at a non-toxic concentration of 0.5 µg/mL during 1 hour of cultivation did not lead to significant changes in cell monolayer, the number of cells and the area of cell bodies did not change. However, the density of the monolayer and the area of the cell field decreased after the incubation. The incubation of cells with nanoparticles led to an increase in the area of the intercellular gate – a location of disruption of cell adhesion, compared to cells without nanoparticles in culture medium. The pre-incubation of rBM-MSCs with nanocrystals caused no changes in the content of total cadherins in the plasma membrane; a decrease in the content of cytoplasmic calreticulin and an increase in the content of surface calreticulin; a decrease in the content of free calcium in the cytoplasm, and an increase in protein-bound intercellular calcium and calcium in the extracellular space. The colocalization analysis revealed that the colocalization of calreticulins with cadherins on the outer surface of the plasma membrane of cells significantly increased after the incubation with GdYVO4:Eu3+ nanocrystals. The paper proposes a possible mechanism of reducing the degree of adhesion by nanocrystals. This study emphasizes the possibility of modulating MSCs adhesion using GdYVO4:Eu3+ nanoparticles. The development of new technologies capable of mitigating adhesion is crucial for the development of regenerative strategies using stem cells.

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Various factors of infectious and toxic genesis can lead to the liver cirrhosis, often accompanied by complications such as recurrent bleeding due to portal hypertension against the background of hepatosplenomegaly. Metabolic changes and disturbances in immunoreactivity occur in the liver and spleen. To substantiate the choice of personalized treatment tactics for patients with hepatosplenomegaly, we investigated individual metabolic predictors and immunopathological processes in patients with: liver cirrhosis and hepatitis B (HBV) and/or hepatitis C (HCV) viruses (I group, n = 52); with herpes viruses CMV (cytomegalovirus) and EBV (Epstein-Barr virus) (II group, n = 48), and with splenomegaly and frequent recurrent bleeding associated with hereditary enzymopathies (III group, n = 15). We used the methods of immunoturbidimetry; enzyme immunoassay; light, fluorescence and confocal microscopy. In group I (HBV/HCV), we revealed a decrease in the C4 component; a significant increase in the phagocytic index and phagocytic number, a reduced number of active phagocytes and the digestion index; a decrease in the IL-1β content and an increase in IL-18 and IL-6. In group II (CMV/EBV), we revealed a high activity of the C3 and a low activity of the C4 component against the background of a high level of ROS in neutrophils; the antineutrophil antibodies (ANCA) formation in 85.7% of patients (71.4% –perinuclear antibodies (pANCA) to myeloperoxidase; 14.3% – cytoplasmic antibodies (CANCA) to proteinase 3). Also, in group II, an increased level of pro-inflammatory cytokines IFN-γ, IL-1β, TNF-α, IL-18 and anti-inflammatory IL-6 was detected. Changes in links of immunity in II group led to the formation of autoimmune reactions in 64.7% of patients, which was expressed in the development of a broad range of antinuclear antibodies ANA (11 specificities, including ANA to chromatin and chromatin-associated proteins, to proteins cytoskeleton, enzymes and enzyme complexes). In group III, we revealed a low absorption capacity of neutrophils, a high frequency of antineutrophil antibodies pANCA occurrence and cANCA (in 67.2% of the examined), and low concentration of TNF-α. The developed model of the stepwise change of immunological markers makes it possible to substantiate the choice of a complex targeted treatment, including antiviral and immunotropic therapy.