Vascular stem/progenitor cell migration induced by smooth muscle cell-derived chemokine (C-C motif) ligand 2 and chemokine (C-X-C motif) ligand 1 contributes to neointima formation

Yu, Baoqi, Wong, Mei Mei, Potter, Claire M. F., Simpson, Russell M. L., Karamariti, Eirini, Zhang, Zhongyi, Zeng, Lingfang, Warren, Derek, Hu, Yanhua, Wang, Wen and Xu, Qingbo (2016) Vascular stem/progenitor cell migration induced by smooth muscle cell-derived chemokine (C-C motif) ligand 2 and chemokine (C-X-C motif) ligand 1 contributes to neointima formation. Stem Cells, 34 (9). pp. 2368-2380. ISSN 1066-5099

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Recent studies have shown that Sca-1+ (stem cell antigen-1) stem/progenitor cells within blood vessel walls may contribute to neointima formation, but the mechanism behind their recruitment has not been explored. In this work Sca-1+ progenitor cells were cultivated from mouse vein graft tissue and found to exhibit increased migration when cocultured with smooth muscle cells (SMCs) or when treated with SMC-derived conditioned medium. This migration was associated with elevated levels of chemokines, CCL2 (chemokine (C-C motif) ligand 2) and CXCL1 (chemokine (C-X-C motif) ligand 1), and their corresponding receptors on Sca-1+ progenitors, CCR2 (chemokine (C-C motif) receptor 2) and CXCR2 (chemokine (C-X-C motif) receptor 2), which were also upregulated following SMC conditioned medium treatment. Knockdown of either receptor in Sca-1+ progenitors significantly inhibited cell migration. The GTPases Cdc42 and Rac1 were activated by both CCL2 and CXCL1 stimulation and p38 phosphorylation was increased. However, only Rac1 inhibition significantly reduced migration and p38 phosphorylation. After Sca-1+ progenitors labeled with green fluorescent protein (GFP) were applied to the adventitial side of wire-injured mouse femoral arteries, a large proportion of GFP-Sca-1+-cells were observed in neointimal lesions, and a marked increase in neointimal lesion formation was seen 1 week post-operation. Interestingly, Sca-1+ progenitor migration from the adventitia to the neointima was abrogated and neointima formation diminished in a wire injury model using CCL2−/− mice. These findings suggest vascular stem/progenitor cell migration from the adventitia to the neointima can be induced by SMC release of chemokines which act via CCR2/Rac1/p38 and CXCR2/Rac1/p38 signaling pathways. Stem Cells 2016;34:2368–2380.

Item Type: Article
Additional Information: © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords: ccl2,cxcl1,migration,smooth muscle cells,progenitor cells
Faculty \ School: Faculty of Science > School of Pharmacy
UEA Research Groups: Faculty of Science > Research Groups > Molecular and Tissue Pharmacology
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Depositing User: Pure Connector
Date Deposited: 23 Nov 2016 00:41
Last Modified: 03 Jul 2023 10:30
DOI: 10.1002/stem.2410


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