A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis

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 microfl...

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Main Authors: Su, Chengxun, Menon, Nishanth Venugopal, Xu, Xiaohan, Teo, Yu Rong, Cao, Huan, Dalan, Rinkoo, Tay, Chor Yong, Hou, Han Wei
Other Authors: School of Mechanical and Aerospace Engineering
Format: Article
Language:English
Published: 2022
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Online Access:https://hdl.handle.net/10356/160379
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1603792022-07-20T06:12:08Z A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis Su, Chengxun Menon, Nishanth Venugopal Xu, Xiaohan Teo, Yu Rong Cao, Huan Dalan, Rinkoo Tay, Chor Yong Hou, Han Wei School of Mechanical and Aerospace Engineering Interdisciplinary Graduate School (IGS) School of Materials Science and Engineering Lee Kong Chian School of Medicine (LKCMedicine) Tan Tock Seng Hospital Science::Biological sciences Extracellular-Matrix Phenotypic Properties 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. Ministry of Education (MOE) Nanyang Technological University National Medical Research Council (NMRC) We would like to acknowledge financial support from the Singapore Ministry of Education Academic Research Fund Tier 1 (RG53/18) awarded to H. W. H., and National Medical Research Council (NMRC) Clinician Scientist Award (CSAINV17nov009) awarded to R. D. C. S. is supported by the NTU Interdisciplinary Graduate Programme Scholarship. H. C. is supported by the NTU Research Scholarship. 2022-07-20T06:12:08Z 2022-07-20T06:12:08Z 2021 Journal Article 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. https://dx.doi.org/10.1039/d1lc00131k 1473-0197 https://hdl.handle.net/10356/160379 10.1039/d1lc00131k 33978037 2-s2.0-85107955949 12 21 2359 2371 en RG53/18 CSAINV17nov009 Lab on a Chip © 2021 The Royal Society of Chemistry. All rights reserved.
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
Extracellular-Matrix
Phenotypic Properties
spellingShingle Science::Biological sciences
Extracellular-Matrix
Phenotypic Properties
Su, Chengxun
Menon, Nishanth Venugopal
Xu, Xiaohan
Teo, Yu Rong
Cao, Huan
Dalan, Rinkoo
Tay, Chor Yong
Hou, Han Wei
A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis
description 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.
author2 School of Mechanical and Aerospace Engineering
author_facet School of Mechanical and Aerospace Engineering
Su, Chengxun
Menon, Nishanth Venugopal
Xu, Xiaohan
Teo, Yu Rong
Cao, Huan
Dalan, Rinkoo
Tay, Chor Yong
Hou, Han Wei
format Article
author Su, Chengxun
Menon, Nishanth Venugopal
Xu, Xiaohan
Teo, Yu Rong
Cao, Huan
Dalan, Rinkoo
Tay, Chor Yong
Hou, Han Wei
author_sort Su, Chengxun
title A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis
title_short A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis
title_full A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis
title_fullStr A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis
title_full_unstemmed A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis
title_sort novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis
publishDate 2022
url https://hdl.handle.net/10356/160379
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