Stem cell-derived exosomes as a biomaterial source for immune modulating therapy

Background: Exosomes, membranous vesicles in the 30~150 nm diameter which secreted by most cell types, are involved in cell-to-cell communications. The vesicles have been reported that they can modulate inflammatory responses in immune cells. Since stem cell derived exosomes has emerged as a new strategy for treating immune disorders accompanying acute inflammatory reactions, we examined their possibility as a biomaterial source for immune modulating therapy using stem cell-derived exosomes. Methods: The immunomodulatory abilities of stem cell-derived conditioned media (SC-CM) were verified by real-time qPCR, western blotting and NO assay. Exosomes from SC-CM were isolated using column chromatographic separation. We analysed the exosomes using dynamic light scattering (DLS), transmission electron microscope (TEM), western blotting (CD9 and CD63 positive extracellular vesicles) and flow cytometry (counting PKH67 labeled vesicles). To determine the anti-inflammatory effects of the NSC derived exosomes, they were incubated with human keratinocyte cell line, HaCaT. Then, proteins within the exosome were identified by tandem mass tagging (TMT) labeling mass spectrophotometry. Results: SC-CM reduced the expression levels of a variety of proinflammatory cytokine and chemokine genes and proteins induced by TNFα and IFNy, and inhibited the phosphorylation of NF-kB and STAT1. Similarly, when the stem cell-derived exosomes were treated to HaCaT cells, they also decreased the pro-inflammatory cytokine and chemokine genes and proteins. We identified several potential factors through proteomics analysis of the exosomes, which may modulate the inflammatory reactions. Summary/Conclusion: Our results show that exosomes can act as potential mediators to inhibit the inflammatory reactions, suggesting that the stem cell-derived exosomes could be used as a new therapeutic biomaterial for the immune-mediated inflammatory diseases, such as autoimmune disorders, cerebrovascular diseases and tumours.