Homotypical Regulation of the Functional Activity of Multipotent Mesenchymal Stromal Cells: The Role of Gap Junctions

• Published in: Cell and tissue biology Vol. 17; no. 2; pp. 122 - 132
• Main Authors: Ezdakova, M. I., Matveeva, D. K., Andreeva, E. R.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 2023; Springer Nature B.V
• Subjects: Angiogenesis; Biomedical and Life Sciences; Cell Biology; Cell migration; Endothelial cells; Flow cytometry; Gap junctions; Immunofluorescence; Interleukin 6; Interleukin 8; Latex beads; Life Sciences; Mesenchymal stem cells; Mitochondria; Paracrine signalling; Phagocytosis; Reactive oxygen species; Stromal cells; Wound healing; intracellular compartments; phagocytosis; homotypic gap junctions; inhibitor; soluble mediators; angiogenesis; multipotent mesenchymal stromal cells; migration
• ISSN: 1990-519X; 1990-5203
• DOI: 10.1134/S1990519X23020049

Perivascular multipotent mesenchymal stromal cells (MSCs) are considered as most likely putative depot for MSCs’ mobilization in the case of tissue damage. Here, we analyzed the involvement of direct homotypic gap junctions (GJs) intercellular communication in realization of MSC functions requested in tissue healing and repair: the state of intracellular compartments; paracrine, in particular, angiogenic, activity, migration and phagocytosis. GJIC in growth arrested MSCs was suppressed using a specific inhibitor, carbenoxolone. Flow cytometry showed a doubling in mitochondrial mass in MSCs with blocked GJs (MitoTracker Green probe). The transmembrane mitochondrial potential (JC-1 probe) and the levels of reactive oxygen species (ROS) (measured using a CM-H2DCFDA probe), as well as the activity of the lysosomal compartment (LysoTracker Green probe), did not change. MSCs with blocked GJs migrated less actively in the wound healing assay. The phagocytosis of latex beads was reduced. According to multiplex immunofluorescence assay, the levels of the IL-6, IL-8, and MCP-3 pleiotropic cytokines were significantly lower in the conditioned medium (CM) from MSCs with blocked GJs. This CM did not stimulate the non-targeted migration of endothelial cells and the growth of the tubule complexes in the chorioallantois membrane of the quail embryo. It has been suggested that a decrease in the efficacy of direct intercellular communication between MSCs and MSCs in vivo may negatively affect both the functioning of stromal cell functions on site as well as their mobilization from tissue depots.