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.

中文翻译：

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外泌体和褪黑激素通过转移miR-34a，miR-124和miR-135b来减轻炎症

间充质干细胞（MSCs）的积极作用主要通过称为旁分泌活性的分子分泌来激活，该分泌调节各种细胞类型（包括免疫细胞）的功能。越来越多的证据表明，尽管尚未阐明确切的潜在机制，但从MSCs释放的可溶性因子的外泌体是基于干细胞治疗的潜在替代药物。这项研究的目的是评估由脂肪来源的MSCs产生的外泌体的潜在作用，并在体内模型中与M2巨噬细胞极化同时检查抗炎基因的变化。分离的外泌体用于研究促炎细胞因子治疗的成纤维细胞和THP-1细胞中的炎症调节。在干扰素γ和肿瘤坏死因子α治疗的炎性环境中外来体处理后，与M2巨噬细胞相关的抗炎mRNA表达显着上调。此外，与外泌体相比，褪黑激素刺激的外泌体通过外泌体miRNAs miR-34a，miR-124和miR-135b发挥了卓越的抗炎调节作用。我们的结果表明，源自脂肪间充质干细胞的褪黑激素刺激的外泌体是再生医学治疗炎性疾病的安全有效工具。与外泌体相比。我们的结果表明，源自脂肪间充质干细胞的褪黑激素刺激的外泌体是再生医学治疗炎性疾病的安全有效工具。与外泌体相比。我们的结果表明，源自脂肪间充质干细胞的褪黑激素刺激的外泌体是再生医学治疗炎性疾病的安全有效工具。