Mesenchymal stem cells exhibit firm adhesion, crawling, spreading and transmigration across aortic endothelial cells: effects of chemokines and shear.
Mesenchymal stem cells exhibit firm adhesion, crawling, spreading and transmigration across aortic endothelial cells: effects of chemokines and shear.
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DOI：
10.1371/journal.pone.0025663
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Middleton J
中科院分区：
文献类型：
--
作者：
Chamberlain G;Smith H;Rainger GE;Middleton J
间充质干细胞（MSC）具有抗炎和免疫抑制特性，可用于治疗动脉硬化等疾病。MSC有一定的能力进入发炎组织，然而，为了利用这一治疗，他们的迁移机制需要阐明。本研究探讨了鼠间充质干细胞（mMSCs）的相互作用，和他们的迁移，鼠主动脉内皮细胞（MAECs），和趋化因子和剪切力的影响。在生理流动条件下检查mMSC与MAEC的相互作用。在连续流动下，mMSC显示缺乏与MAEC的相互作用。然而，当流动停止（10分钟）然后开始时，mMSC粘附并在内皮表面上爬行，延伸细微绒毛突起（丝状伪足）。然后，它们向多个方向扩散延伸伪足。CXCL9能显著提高mMSCs的粘附、爬行和伸展率，剪切力能显著促进mMSCs的爬行和伸展。CXCL9、CXCL16、CCL20和CCL25显著增强跨MAEC的跨内皮迁移。迁移的mMSCs具有下调的受体CXCR3、CXCR6、CCR6和CCR9。这项研究进一步了解MSC跨内皮迁移和趋化因子和剪切应力的影响，这是相关的炎症性疾病，如动脉硬化。
Mesenchymal stem cells (MSCs) have anti-inflammatory and immunosuppressive properties and may be useful in the therapy of diseases such as arteriosclerosis. MSCs have some ability to traffic into inflamed tissues, however to exploit this therapeutically their migratory mechanisms need to be elucidated. This study examines the interaction of murine MSCs (mMSCs) with, and their migration across, murine aortic endothelial cells (MAECs), and the effects of chemokines and shear stress. The interaction of mMSCs with MAECs was examined under physiological flow conditions. mMSCs showed lack of interaction with MAECs under continuous flow. However, when the flow was stopped (for 10min) and then started, mMSCs adhered and crawled on the endothelial surface, extending fine microvillous processes (filopodia). They then spread extending pseudopodia in multiple directions. CXCL9 significantly enhanced the percentage of mMSCs adhering, crawling and spreading and shear forces markedly stimulated crawling and spreading. CXCL9, CXCL16, CCL20 and CCL25 significantly enhanced transendothelial migration across MAECs. The transmigrated mMSCs had down-regulated receptors CXCR3, CXCR6, CCR6 and CCR9. This study furthers the knowledge of MSC transendothelial migration and the effects of chemokines and shear stress which is of relevance to inflammatory diseases such as arteriosclerosis.