Abstract
The positive effects of mesenchymal stem cells (MSCs) are primarily activated through molecular secretions known as paracrine activity, which regulates the function of various cell types including immune cells. Accumulating evidence shows that exosomes of soluble factors released from MSCs are potential alternative agents for stem cell-based therapy, although the exact underlying mechanism has not been elucidated. The purpose of this study was to evaluate the potential effects of exosomes produced by adipose-derived MSCs and to examine the changes in anti-inflammatory genes in concurrence with the polarization of M2 macrophages in cellular models ex vivo. Isolated exosomes were used to investigate the inflammatory modulation in pro-inflammatory cytokine-treated fibroblasts and THP-1 cells. The anti-inflammatory mRNA expression associated with M2 macrophages was significantly upregulated after exosome treatment in an interferon gamma and tumor necrosis factor alpha-treated inflammatory environment. Furthermore, melatonin-stimulated exosomes exerted superior anti-inflammatory modulation via exosomal miRNAs miR-34a, miR-124, and miR-135b, compared with exosomes. Our results indicate that melatonin-stimulated exosomes originating from adipose-derived MSCs are safe and efficient tools for regenerative medicine to treat inflammatory diseases.
Highlights
Mesenchymal stem cells (MSCs) are promising cell sources owing to their multipotent and immunosuppressive properties [1]
We examined the antiinflammatory properties of exosomes secreted from adipose MSCs, using fibroblasts and THP-1 cells treated with proinflammatory cytokines interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα)
MSCs were isolated from the adipose tissue of healthy human donors
Summary
Mesenchymal stem cells (MSCs) are promising cell sources owing to their multipotent and immunosuppressive properties [1]. Accumulating evidence shows that MSCs exert antiinflammatory effects by modulating immune cells and the inflammatory environment [2]. Among the trophic factors of MSCs, exosomes have attracted much attention as new mediators in cell-to-cell interactions [6]. Exosomes originating from the endosomal pathway contain biological factors such as proteins, lipids, and nucleic acids that mediate intercellular communication [7]. MSCderived exosomes can promote phenotypic and functional changes in the surrounding cells and microenvironment by inducing the activation of regenerative events [8]. Recent studies have demonstrated that exosomes play important roles in the regulation of inflammatory phenotypes via M2 macrophage polarization [9, 10]. An exact understanding of the immunomodulatory effects of exosomes is essential to develop more efficient therapeutic strategies for curing intractable or chronic inflammatory diseases
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