Novel Marine Organism-Derived Extracellular Vesicles for Control of Anti-Inflammation

BACKGROUND Extracellular vesicles (EVs) exhibit potential as functional biomolecules for tissue regeneration and immunomodulation as they play important roles in the physiological communication between cells. EV internal cargo contains miRNAs, proteins, lipids, and so on. Osteoarthritis (OA) is a common joint disease causing disability owing to impaired joint function and pain. EVs originating from animal cells and tissue matrices are also being considered for OA, in addition to research involving non-steroidal therapeutic agents. However, there are no studies on EVs from marine organisms. Hence, we focused on sea cucumber-derived EVs and conducted experiments to set up an extraction protocol and to demonstrate their efficacy to modulate the inflammatory environment. METHODS Sea cucumber extracellular matrices (SECMs) were prepared by a decellularization process. Lyophilized SECMs were treated with collagenase and filtered to isolate sea cucumber extracellular vesicles (SEVs). After isolation, we conducted physical characterization and cell activation studies including cytotoxicity, proliferation, and anti-inflammation effect assays. RESULTS The physical characterization results showed circular SEVs in the size range of 66-480 nm. These SEVs contained large amounts of protein cargo, infiltrated the synoviocyte membrane without damage, and had a suppressive effect on inflammatory cytokines. CONCLUSION This study established an extraction process for EVs from sea cucumber and reported the anti-inflammatory ability of SEVs. Isolated SEVs can be further utilized for tissue regeneration studies and can be compared to various marine or animal-derived EVs.