Mesenchymal Stem Cells Secrete Immunologically Active Exosomes
Mesenchymal Stem Cells Secrete Immunologically Active Exosomes
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DOI：
10.1089/scd.2013.0479
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发表时间：
2014-06-01
影响因子：
4
通讯作者：
Lim, Sai Kiang
中科院分区：
文献类型：
--
作者：
Zhang, Bin;Yin, Yijun;Lim, Sai Kiang
间充质干细胞（MSC）已被证明分泌具有心脏保护作用的外泌体。在这里，我们证明了MSC外泌体，一种分泌的膜囊泡，具有免疫活性。MSC外泌体在THP 1-Xblue（一种具有NF kB-SEAP报告基因的THP-1报告细胞系）中诱导多粘菌素抗性、MYD 88依赖性分泌型胚胎碱性磷酸酶（SEAP）表达。与脂多糖相比，它们在3和72 h诱导高水平的抗炎性IL 10和TGF β 1转录物，并且在3 h显著减弱促炎性IL 1B、IL 6、TNFA和IL 12 P40转录物的水平。MyD 88缺陷可使细胞因子转录的3-h诱导而非72-h诱导消失。原代人和小鼠单核细胞表现出相似的外泌体诱导的细胞因子转录谱。外泌体处理的THP-1而非MyD 88缺陷型THP-1细胞将活化的CD 4（+）T细胞极化为CD 4（+）CD 25（+）FoxP 3（+）调节性T细胞（TCLs），比例为1个外泌体处理的THP-1细胞比1，000个CD 4（+）T细胞。MSC外泌体的输注增强了小鼠中同种异体皮肤移植物的存活并增加了TBI。
Mesenchymal stem cells (MSCs) have been shown to secrete exosomes that are cardioprotective. Here, we demonstrated that MSC exosome, a secreted membrane vesicle, is immunologically active. MSC exosomes induced polymyxin-resistant, MYD88-dependent secreted embryonic alkaline phosphatase (SEAP) expression in a THP1-Xblue, a THP-1 reporter cell line with an NFkB-SEAP reporter gene. In contrast to lipopolysaccharide, they induced high levels of anti-inflammatory IL10 and TGF beta 1 transcript at 3 and 72 h, and much attenuated levels of pro-inflammatory IL1B, IL6, TNFA and IL12P40 transcript at 3-h. The 3-h but not 72-h induction of cytokine transcript was abrogated by MyD88 deficiency. Primary human and mouse monocytes exhibited a similar exosome-induced cytokine transcript profile. Exosome-treated THP-1 but not MyD88-deficient THP-1 cells polarized activated CD4(+) T cells to CD4(+) CD25(+) FoxP3(+) regulatory T cells (Tregs) at a ratio of one exosome-treated THP-1 cell to 1,000 CD4(+) T cells. Infusion of MSC exosomes enhanced the survival of allogenic skin graft in mice and increased Tregs.