Cell Therapy Center, Severance Hospital, Seoul 03722, Republic of Korea.
Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, Seoul 02841, Republic of Korea.
Biomed Res Int. 2020 Nov 24;2020:1621394. doi: 10.1155/2020/1621394. eCollection 2020.
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.
间充质干细胞（MSCs）的积极作用主要通过称为旁分泌作用的分子分泌来激活，旁分泌作用调节包括免疫细胞在内的各种细胞类型的功能。越来越多的证据表明，MSCs 释放的可溶性因子的外泌体是基于干细胞的治疗的潜在替代药物，尽管确切的潜在机制尚未阐明。本研究的目的是评估脂肪来源的 MSC 产生的外泌体的潜在作用，并研究与 M2 巨噬细胞极化同时发生的抗炎基因的变化在体外细胞模型中。分离的外泌体用于研究在促炎细胞因子处理的成纤维细胞和 THP-1 细胞中的炎症调节。在干扰素 γ和肿瘤坏死因子 α处理的炎症环境中，外泌体处理后，与 M2 巨噬细胞相关的抗炎 mRNA 表达明显上调。此外，与外泌体相比，褪黑素刺激的外泌体通过外泌体 miRNAs miR-34a、miR-124 和 miR-135b 发挥更好的抗炎调节作用。我们的结果表明，来自脂肪来源的 MSC 的褪黑素刺激的外泌体是治疗炎症性疾病的再生医学的安全有效的工具。
