Controlling the Immune Response to Zebrafish Spinal Cord Injury Via Extracellular Vesicles Secreted by Activated Monocyte-like Cells

The immune response to spinal cord injury (SCI) is implemented via local and systemic inflammation, followed by repair and functional recovery of damaged organs. The possibility to control pro-inflammatory activity and stimulate regenerative processes is an important aspect of the research. Extracellular vesicles (EVs) secreted by activated monocyte-like cells may be a useful tool to drive immune response polarization toward M1 or M2 macrophages. The aim of the study was to investigate the systemic effects of extracellular vesicles, produced by activated monocyte-like cells of the THP-1 line, when simulating SCI in the zebrafish Danio rerio. It was shown that intracoelomic infusion of EVs, secreted by tumor necrosis factor (TNF)-activated THP-1 cells, to zebrafish with SCI led to a pro-inflammatory effect, manifested by an increase in the expression of il-6 and tnf-α genes in the brain tissue, and to a less pronounced change in their activity in the heart, liver and kidney tissues. At the same time, EVs, secreted by non-activated and phorbol-12-myristate-13-acetate (PMA)-activated THP-1 cells, did not exhibit any activity. Thus, it was demonstrated that extracellular vesicles secreted by activated monocyte-like cells have the potential to manage immune response after simulated spinal cord injury in zebrafish.