Characterization of inflammatory factor-induced changes in mesenchymal stem cell exosomes and sequencing analysis of exosomal microRNAs

BACKGROUND: Treatments utilizing stems cells often require stem cells to be exposed to inflammatory environments, but the effects of such environments are unknown. AIM: To examine the effects of inflammatory cytokines on the morphology and quantity of mesenchymal stem cell exosomes (MSCs-exo) as well as the differential expression of microRNAs (miRNAs) in the exosomes. METHODS: tube formation assays and Western blot were performed in endothelial cells which were used to assess the angiogenic potential of MSCs-exo after inflammatory cytokine stimulation. RESULTS: MSCs-exo were numerous, small, and regularly shaped in the VCAM-1 group. TNFα stimulated MSCs to secrete larger and irregular exosomes. IL6 led to a reduced quantity of MSCs-exo. Compared to the control group, the TNFα and IL6 groups had more downregulated differentially expressed miRNAs, particularly angiogenesis-related miRNAs. The angiogenic potential of MSCs-exo declined after IL6 stimulation. CONCLUSION: TNFα and IL6 may influence the expression of miRNAs that down-regulate the PI3K-AKT, MAPK, and VEGF signaling pathways; particularly, IL6 significantly down-regulates the PI3K-AKT signaling pathway. Overall, inflammatory cytokines may lead to changes in exosomal miRNAs that abnormally impact cellular components, molecular function, and biological processes.