Human mesenchymal stem cell microvesicles for treatment of Escherichia coli endotoxin-induced acute lung injury in mice.
Human mesenchymal stem cell microvesicles for treatment of Escherichia coli endotoxin-induced acute lung injury in mice.
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DOI：
10.1002/stem.1504
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发表时间：
2014-01
期刊：
影响因子：
5.2
通讯作者：
Lee, Jae W.
中科院分区：
文献类型：
--
作者：
Zhu, Ying-gang;Feng, Xiao-mei;Abbott, Jason;Fang, Xiao-hui;Hao, Qi;Monsel, Antoine;Qu, Jie-ming;Matthay, Michael A.;Lee, Jae W.
关键词：
我们先前发现，在离体灌注的人肺中，人间充质干细胞（MSC）或其条件培养基部分地通过分泌可溶性因子如角质形成细胞生长因子（KGF）来恢复大肠杆菌内毒素诱导的急性肺损伤（ALI）后的肺蛋白渗透性并减少肺泡炎症。最近，MSC被发现释放微泡（MV）的生物活性，因为存在的mRNA或miRNA的修复性能。MV是作为外泌体从内体区室释放或从表面膜脱落的膜的环状片段。目前的研究旨在确定由人骨髓来源的MSC释放的MV是否能有效恢复C57 BL/6小鼠中大肠杆菌内毒素诱导的ALI中的肺蛋白渗透性并减少炎症。MVs气管内滴注可改善ALI 48 h的多项指标。与内毒素损伤的小鼠相比，MV使血管外肺水减少了43%，使支气管肺泡灌洗液（BAL）中的总蛋白水平减少了35%，表明肺水肿和肺蛋白渗透性降低。MV还使BAL液中中性粒细胞和巨噬细胞炎性蛋白-2水平的流入分别降低了73%和49%，表明炎症减轻。KGF siRNA预处理MSC部分消除了MSC释放的MV的治疗作用，表明KGF蛋白表达对于潜在机制是重要的。总之，人MSC衍生的微泡在小鼠中大肠杆菌内毒素诱导的ALI后部分地通过在受损肺泡中表达KGF mRNA而具有治疗有效性。
We previously found that human mesenchymal stem cells (MSC) or its conditioned medium restored lung protein permeability and reduced alveolar inflammation following E.coli endotoxin-induced acute lung injury (ALI) in an ex vivo perfused human lung in part through the secretion of soluble factors such as keratinocyte growth factor (KGF). Recently, MSC were found to release microvesicles (MV) that were biologically active because of the presence of mRNA or miRNA with reparative properties. MVs are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the surface membranes. The current studies were designed to determine if MVs released by human bone marrow derived MSCs would be effective in restoring lung protein permeability and reducing inflammation in E.coli endotoxin-induced ALI in C57BL/6 mice. The intra-tracheal instillation of MVs improved several indices of ALI at 48 h. Compared to endotoxin-injured mice, MVs reduced extravascular lung water by 43% and reduced total protein levels in the bronchoalveolar lavage (BAL) fluid by 35%, demonstrating a reduction in pulmonary edema and lung protein permeability. MVs also reduced the influx of neutrophils and macrophage inflammatory protein-2 levels in the BAL fluid by 73% and 49% respectively, demonstrating a reduction in inflammation. KGF siRNA-pretreatment of MSC partially eliminated the therapeutic effects of MVs released by MSCs, suggesting that KGF protein expression was important for the underlying mechanism. In summary, human MSC derived microvesicles were therapeutically effective following E.coli endotoxin-induced ALI in mice in part through the expression of KGF mRNA in the injured alveolus.
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影响因子：
3.7
作者：
Bruno S;Grange C;Collino F;Deregibus MC;Cantaluppi V;Biancone L;Tetta C;Camussi G
通讯作者：
Camussi G
DOI：
10.1152/ajplung.2000.279.6.l1199
发表时间：
2000-12-01
影响因子：
4.9
作者：
Viget, NB;Guery, BPH;Pittet, JF
通讯作者：
Pittet, JF
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
20.3
作者：
Deregibus, Maria Chiara;Cantaluppi, Vincenzo;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
6.1
作者：
Gatti, Stefano;Bruno, Stefania;Camussi, Giovanni
通讯作者：
Camussi, Giovanni