Exosomes derived from human menstrual blood-derived stem cells alleviate fulminant hepatic failure.
Exosomes derived from human menstrual blood-derived stem cells alleviate fulminant hepatic failure.
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源自人类月经血液细胞的外泌体减轻了暴发性肝衰竭。
DOI：
10.1186/s13287-016-0453-6
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发表时间：
2017-01-23
影响因子：
7.5
通讯作者：
Xiang C
中科院分区：
文献类型：
--
作者：
Chen L;Xiang B;Wang X;Xiang C
人月经血来源的干细胞（MenSC）是一种新的MSC来源，具有易于收集和分离的优点。外泌体含有一些mRNA和粘附分子，可能会影响细胞和动物生理学。本研究旨在研究MenSC衍生的外泌体（MenSC-Ex）对AML 12细胞（体外）和D-GalN/LPS诱导的FHF小鼠（体内）的治疗潜力。透射电镜和Western blot鉴定MenSC-Ex。抗体阵列用于检查MenSC-Ex上的细胞因子水平。MenSC-Ex在体外在D-GalN/LPS诱导的AML 12中处理。检测细胞增殖和凋亡。在用D-GalN/LPS处理之前24小时将MenSC-Ex注射到小鼠的尾静脉中。以血液和肝组织作为生理生化指标。通过测定肝细胞单个核细胞（MNCs）数量和凋亡蛋白caspase-3的含量来阐明其保肝作用的机制。人月经血来源的干细胞来源的外泌体（MenSC-Ex）是具有直径约30-100 nm的圆形球状形状的双脂质膜囊泡。细胞因子阵列显示MenSC-Ex表达细胞因子，包括ICAM-1、血管生成素-2、Axl、血管生成素、IGFBP-6、骨保护素、IL-6和IL-8。MenSC-Ex在移植后6 h明显改善肝功能，提高存活率，抑制肝细胞凋亡。MenSC-Ex分别迁移至损伤部位和AML 12细胞（小鼠肝细胞系）。此外，MenSC-Ex减少了肝脏单核细胞（MNCs）的数量和受损肝脏中活性凋亡蛋白caspase-3的数量。总之，我们的研究结果为MenSC-Ex在FHF中的抗凋亡能力提供了初步证据，并表明MenSC-Ex可能是治疗FHF的替代治疗方法。本文的在线版本（doi：10.1186/s13287-016-0453-6）包含补充材料，可供授权用户使用。
Human menstrual blood-derived stem cells (MenSCs) are a novel source of MSCs that provide the advantage of being easy to collect and isolate. Exosomes contain some mRNAs and adhesion molecules that can potentially impact cellular and animal physiology. This study aimed to investigate the therapeutic potential of MenSC-derived exosomes (MenSC-Ex) on AML12 cells (in vitro) and D-GalN/LPS-induced FHF mice (in vivo). Transmission electron microscopy and Western blot were used to identify MenSC-Ex. Antibody array was used to examine cytokine levels on MenSC-Ex. MenSC-Ex were treated in D-GalN/LPS-induced AML12 in vitro. Cell proliferation and apoptosis were measured. MenSC-Ex were injected into the tail veins of mice 24 h before treatment with D-GalN/LPS. Blood and liver tissues served as physiological and biochemical indexes. The number of liver mononuclear cells (MNCs) and the amount of the active apoptotic protein caspase-3 were determined to elaborate the mechanism of hepatoprotective activity. Human menstrual blood-derived stem cell-derived exosomes (MenSC-Ex) are bi-lipid membrane vesicles that have a round, ball-like shape with a diameter of approximately 30–100 nm. Cytokine arrays have shown that MenSC-Ex expressed cytokines, including ICAM-1, angiopoietin-2, Axl, angiogenin, IGFBP-6, osteoprotegerin, IL-6, and IL-8. MenSC-Ex markedly improved liver function, enhanced survival rates, and inhibited liver cell apoptosis at 6 h after transplantation. MenSC-Ex migrated to sites of injury and to AML12 cells (a mouse hepatocyte cell line), respectively. Moreover, MenSC-Ex reduced the number of liver mononuclear cells (MNCs) and the amount of the active apoptotic protein caspase-3 in injured livers. In conclusion, our results provide preliminary evidence for the anti-apoptotic capacity of MenSC-Ex in FHF and suggest that MenSC-Ex may be an alternative therapeutic approach to treat FHF. The online version of this article (doi:10.1186/s13287-016-0453-6) contains supplementary material, which is available to authorized users.