Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through Exosomes
Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through Exosomes
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DOI：
10.1155/2019/7921760
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发表时间：
2019-11-05
影响因子：
4.3
通讯作者：
Kim, Hyun Ok
中科院分区：
文献类型：
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作者：
Heo, June Seok;Choi, Youjeong;Kim, Hyun Ok
越来越多的证据表明，来自间充质干细胞（MSCs）的旁分泌因子能够通过与各种免疫细胞的相互作用来调节免疫系统。本研究分离培养了脂肪源性间充质干细胞（AdMSCs）和人外周血单核细胞（PBMCs），研究了间充质干细胞诱导的巨噬细胞（iM phi）对炎症和免疫调节的影响。与MSCs间接共培养增加了pbmc中活化的M2巨噬细胞标记物精氨酸酶-1和甘露糖受体（CD206）的表达，表明MSCs分泌的因子促进了M2- m phi极化。此外，与其他组（仅AdMSCs， AdMSCs加iM phi）相比，iM phi对活化T细胞的生长表现出类似的更高的抑制作用，这意味着iM phi可以发挥足够的功能作用。有趣的是，当与iM phi共培养时，FoxP3的Treg细胞数量显著增加，这表明iM phi通过调节FoxP3的表达对Treg细胞具有免疫调节作用。值得注意的是，iM phi表达高水平的免疫抑制和抗炎细胞因子，即IL-10和TSG-6。此外，我们证实了admsc衍生的外泌体通过上调M2巨噬细胞标志物的表达来调节巨噬细胞极化。最后，我们的研究结果表明，iM - phi在调节免疫调节和炎症介导的反应中发挥重要作用。因此，iM - phi可能被用作一种新的基于干细胞的无细胞疗法，用于治疗免疫介导的炎症性疾病。
Accumulating evidence has shown that the paracrine factors derived from mesenchymal stem cells (MSCs) are capable of regulating the immune system via interaction with various immune cells. In this study, adipose-derived MSCs (AdMSCs) and human peripheral blood monocytes (PBMCs) were isolated and cultured to examine the effects of MSC-induced macrophages (iM phi) on inflammation and immune modulation. Indirect coculture with MSCs increased the expression of arginase-1 and mannose receptor (CD206), markers of activated M2 macrophages, in the PBMCs demonstrating that MSC-secreted factors promoted M2-M phi polarization. Additionally, iM phi exhibited a similar higher inhibitory effect on the growth of activated T cells compared to that in the other groups (AdMSCs only, AdMSCs plus iM phi), implying that iM phi can play a sufficient functional role. Interestingly, the population of FoxP3 Treg cells significantly increased when cocultured with iM phi, suggesting that iM phi have an immunomodulatory effect on the Treg cells through the modulation of the FoxP3 expression. Notably, iM phi expressed high levels of immunosuppressive and anti-inflammatory cytokines, namely IL-10 and TSG-6. Furthermore, we confirmed that the AdMSC-derived exosomes modulated macrophage polarization by upregulating the expression of M2 macrophage markers. Conclusively, our results suggest that iM phi play a significant role in regulating the immunomodulatory- and inflammatory-mediated responses. Thus, iM phi may be used as a novel stem cell-based cell-free therapy for the treatment of immune-mediated inflammatory disorders.