Extracellular vesicles derived from DFO-preconditioned canine AT-MSCs reprogram macrophages into M2 phase

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Mesenchymal stem/stromal cells (MSCs) are effective therapeutic agents that ameliorate inflammation through paracrine effect; in this regard, extracellular vesicles (EVs) have been frequently studied. To improve the secretion of anti-inflammatory factors from MSCs, preconditioning with hypoxia or hypoxia-mimetic agents has been attempted and the molecular changes in preconditioned MSC-derived EVs explored. In this study, we aimed to investigate the increase of hypoxia-inducible factor 1-alpha (HIF-1α)/cyclooxygenase-2 (COX-2) in deferoxamine (DFO)-preconditioned canine MSC (MSCDFO) and whether these molecular changes were reflected on EVs. Furthermore, we focused on MSCDFO derived EVs (EVDFO) could affect macrophage polarization via the transfer function of EVs. Results In MSCDFO, accumulation of HIF-1α were increased and production of COX-2 were activated. Also, Inside of EVDFO were enriched with COX-2 protein. To evaluate the transferring effect of EVs to macrophage, the canine macrophage cell line, DH82, was treated with EVs after lipopolysaccharide (LPS) stimulation. Polarization changes of DH82 were evaluated with quantitative real-time PCR and immunofluorescence analyses. When LPS-induced DH82 was treated with EVDFO, phosphorylation of signal transducer and transcription3 (p-STAT3), which is one of key factor of inducing M2 phase, expression was increased in DH

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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