Immune regulation is more effective in the U937 inflammation model with mesenchymal stem cell extracellular vesicles stimulated by pro-inflammatory cytokines

Mesenchymal stem cells (MSCs), which are multipotent adult cells with many therapeutic effects, can be derived from stromal tissues. MSCs also exert immunoregulatory effects through extracellular vesicles (EVs), cell membrane structures that carry paracrine factors. It is thought that the mediators (cytokines, growth factors, etc.) secreted by stem cells change under inflammatory conditions, and the therapeutic activity of MSCs increases. The purpose of this study was to investigate the possible effects of stimulated human Wharton's jelly-derived mesenchymal stem cell extracellular vesicles, obtained with or without stimulation with inflammatory cytokines, on inflammation. The study aimed to determine the effects of pro-inflammatory cytokines interleukin 1 <i>β</i> (IL-1 <i>β</i>), interferon <i>γ</i> (IFN-<i>γ</i>), and tumor necrosis factor <i>α</i> (TNF-<i>α</i>) stimulated extracellular vesicles (sEVs) on the inflammation model U937 macrophages induced by phorbol-12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS) treatment. Experimental studies were designed to investigate the effects of EVs obtained without stimulation with inflammatory cytokines and those obtained after stimulation with inflammatory cytokines in the macrophage cell line U937. Flow cytometry, gene expression, and immunofluorescence analyses were performed to investigate the apoptotic and antiproliferative effects of EVs and sEVs in the U937 macrophage inflammation model. WJ-MSC EVs obtained after culture with inflammatory cytokines had a greater apoptotic effect on U937 cells and reduced inflammatory cytokine release than EVs cultured in standard medium.