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Title: A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis
Authors: Su, Chengxun
Menon, Nishanth Venugopal
Xu, Xiaohan
Teo, Yu Rong
Cao, Huan
Dalan, Rinkoo
Tay, Chor Yong
Hou, Han Wei
Keywords: Science::Biological sciences
Issue Date: 2021
Source: Su, C., Menon, N. V., Xu, X., Teo, Y. R., Cao, H., Dalan, R., Tay, C. Y. & Hou, H. W. (2021). A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis. Lab On a Chip, 21(12), 2359-2371.
Project: RG53/18
Journal: Lab on a Chip
Abstract: Mechanistic understanding of atherosclerosis is largely hampered by the lack of a suitable in vitro human arterial model that recapitulates the arterial wall structure, and the interplay between different cell types and the surrounding extracellular matrix (ECM). This work introduces a novel microfluidic endothelial cell (EC)-smooth muscle cell (SMC) 3D co-culture platform that replicates the structural and biological aspects of the human arterial wall for modeling early atherosclerosis. Using a modified surface tension-based ECM patterning method, we established a well-defined intima-media-like structure, and identified an ECM composition (collagen I and Matrigel mixture) that retains the SMCs in a quiescent and aligned state, characteristic of a healthy artery. Endothelial stimulation with cytokines (IL-1β and TNFα) and oxidized low-density lipoprotein (oxLDL) was performed on-chip to study various early atherogenic events including endothelial inflammation (ICAM-1 expression), EC/SMC oxLDL uptake, SMC migration, and monocyte-EC adhesion. As a proof-of-concept for drug screening applications, we demonstrated the atheroprotective effects of vitamin D (1,25(OH)2D3) and metformin in mitigating cytokine-induced monocyte-EC adhesion and SMC migration. Overall, the developed arterial wall model facilitates quantitative and multi-factorial studies of EC and SMC phenotype in an atherogenic environment, and can be readily used as a platform technology to reconstitute multi-layered ECM tissue biointerfaces.
ISSN: 1473-0197
DOI: 10.1039/d1lc00131k
Schools: School of Mechanical and Aerospace Engineering 
Interdisciplinary Graduate School (IGS) 
School of Materials Science and Engineering 
Lee Kong Chian School of Medicine (LKCMedicine) 
Organisations: Tan Tock Seng Hospital
Rights: © 2021 The Royal Society of Chemistry. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:IGS Journal Articles
LKCMedicine Journal Articles
MAE Journal Articles
MSE Journal Articles

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