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 implementedvia local and systemic inflammation, followed by repair and functionalrecovery of damaged organs. The possibility to control pro-inflammatoryactivity and stimulate regenerative processes is an important aspectof the research. Extracellular vesicles (EVs) secreted by activatedmonocyte-like cells may be a useful tool to drive immune responsepolarization toward M1 or M2 macrophages. The aim of the study wasto investigate the systemic effects of extracellular vesicles, producedby activated monocyte-like cells of the THP-1 line, when simulatingSCI in the zebrafish Danio rerio.It was shown that intracoelomic infusion of EVs, secreted by tumornecrosis factor (TNF)-activated THP-1 cells, to zebrafish with SCIled to a pro-inflammatory effect, manifested by an increase in theexpression 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-activatedand phorbol-12-myristate-13-acetate (PMA)-activated THP-1 cells,did not exhibit any activity. Thus, it was demonstrated that extracellularvesicles secreted by activated monocyte-like cells have the potentialto manage immune response after simulated spinal cord injury inzebrafish.