Mesenchymal stem cells exhibit firm adhesion, crawling, spreading and transmigration across aortic endothelial cells: effects of chemokines and shear

• Published in: PloS one 2011-09, Vol.6 (9), p.e25663
• Main Authors: Chamberlain, Giselle, Smith, Helen, Rainger, G Ed, Middleton, Jim
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Aorta; Aorta - cytology; Arteriosclerosis; Arthritis; Atherosclerosis; Biology; Cardiomyocytes; CCL20 protein; CCR6 protein; CCR9 protein; Cell Adhesion - drug effects; Chemokines; Chemokines - pharmacology; Chemotaxis - drug effects; Continuous flow; CXCL16 protein; CXCR3 protein; Dentistry; Down-Regulation - drug effects; Emigration; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelium; Filopodia; Heart attacks; Hospitals; Immunosuppression; Inflammation; Inflammatory diseases; Leukocyte migration; Ligands; Mechanical stimuli; Medicine; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; Mesenchyme; Mice; Neutrophils; Physiological aspects; Receptors; Receptors, Chemokine - metabolism; Recruitment; Shear stress; Spreading; Stem cell transplantation; Stem cells; Stress, Mechanical; Tissues; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0025663

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 10 min) 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.