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A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions
Cell signalling and mechanics influence vascular pathophysiology and there is an increasing demand for in vitro model systems that enable examination of signalling between vascular cells under hemodynamic conditions. Current 3D vessel wall constructs do not recapitulate the mechanical conditions of...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Royal Society of Chemistry
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972738/ https://www.ncbi.nlm.nih.gov/pubmed/29756630 http://dx.doi.org/10.1039/c8lc00286j |
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author | van Engeland, Nicole C. A. Pollet, Andreas M. A. O. den Toonder, Jaap M. J. Bouten, Carlijn V. C. Stassen, Oscar M. J. A. Sahlgren, Cecilia M. |
author_facet | van Engeland, Nicole C. A. Pollet, Andreas M. A. O. den Toonder, Jaap M. J. Bouten, Carlijn V. C. Stassen, Oscar M. J. A. Sahlgren, Cecilia M. |
author_sort | van Engeland, Nicole C. A. |
collection | PubMed |
description | Cell signalling and mechanics influence vascular pathophysiology and there is an increasing demand for in vitro model systems that enable examination of signalling between vascular cells under hemodynamic conditions. Current 3D vessel wall constructs do not recapitulate the mechanical conditions of the native tissue nor do they allow examination of cell–cell interactions under relevant hemodynamic conditions. Here, we describe a 3D microfluidic chip model of arterial endothelial and smooth muscle cells where cellular organization, composition and interactions, as well as the mechanical environment of the arterial wall are mimicked. The hemodynamic EC–VSMC-signalling-on-a-chip consists of two parallel polydimethylsiloxane (PDMS) cell culture channels, separated by a flexible, porous PDMS membrane, mimicking the porosity of the internal elastic lamina. The hemodynamic EC–VSMC-signalling-on-a-chip allows co-culturing of human aortic endothelial cells (ECs) and human aortic vascular smooth muscle cells (VSMCs), separated by a porous membrane, which enables EC–VSMC interaction and signalling, crucial for the development and homeostasis of the vessel wall. The device allows real time cell imaging and control of hemodynamic conditions. The culture channels are surrounded on either side by vacuum channels to induce cyclic strain by applying cyclic suction, resulting in mechanical stretching and relaxation of the membrane in the cell culture channels. The blood flow is mimicked by creating a flow of medium at the EC side. Vascular cells remain viable during prolonged culturing, exhibit physiological morphology and organization and make cell–cell contact. During dynamic culturing of the device with a shear stress of 1–1.5 Pa and strain of 5–8%, VSMCs align perpendicular to the given strain in the direction of the flow and EC adopt a cobblestone morphology. To our knowledge, this is the first report on the development of a microfluidic device, which enables a co-culture of interacting ECs and VSMCs under hemodynamic conditions and presents a novel approach to systematically study the biological and mechanical components of the intimal-medial vascular unit. |
format | Online Article Text |
id | pubmed-5972738 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-59727382018-06-13 A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions van Engeland, Nicole C. A. Pollet, Andreas M. A. O. den Toonder, Jaap M. J. Bouten, Carlijn V. C. Stassen, Oscar M. J. A. Sahlgren, Cecilia M. Lab Chip Chemistry Cell signalling and mechanics influence vascular pathophysiology and there is an increasing demand for in vitro model systems that enable examination of signalling between vascular cells under hemodynamic conditions. Current 3D vessel wall constructs do not recapitulate the mechanical conditions of the native tissue nor do they allow examination of cell–cell interactions under relevant hemodynamic conditions. Here, we describe a 3D microfluidic chip model of arterial endothelial and smooth muscle cells where cellular organization, composition and interactions, as well as the mechanical environment of the arterial wall are mimicked. The hemodynamic EC–VSMC-signalling-on-a-chip consists of two parallel polydimethylsiloxane (PDMS) cell culture channels, separated by a flexible, porous PDMS membrane, mimicking the porosity of the internal elastic lamina. The hemodynamic EC–VSMC-signalling-on-a-chip allows co-culturing of human aortic endothelial cells (ECs) and human aortic vascular smooth muscle cells (VSMCs), separated by a porous membrane, which enables EC–VSMC interaction and signalling, crucial for the development and homeostasis of the vessel wall. The device allows real time cell imaging and control of hemodynamic conditions. The culture channels are surrounded on either side by vacuum channels to induce cyclic strain by applying cyclic suction, resulting in mechanical stretching and relaxation of the membrane in the cell culture channels. The blood flow is mimicked by creating a flow of medium at the EC side. Vascular cells remain viable during prolonged culturing, exhibit physiological morphology and organization and make cell–cell contact. During dynamic culturing of the device with a shear stress of 1–1.5 Pa and strain of 5–8%, VSMCs align perpendicular to the given strain in the direction of the flow and EC adopt a cobblestone morphology. To our knowledge, this is the first report on the development of a microfluidic device, which enables a co-culture of interacting ECs and VSMCs under hemodynamic conditions and presents a novel approach to systematically study the biological and mechanical components of the intimal-medial vascular unit. Royal Society of Chemistry 2018-06-07 2018-05-14 /pmc/articles/PMC5972738/ /pubmed/29756630 http://dx.doi.org/10.1039/c8lc00286j Text en This journal is © The Royal Society of Chemistry 2018 http://creativecommons.org/licenses/by-nc/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported Licence (CC BY-NC 3.0) |
spellingShingle | Chemistry van Engeland, Nicole C. A. Pollet, Andreas M. A. O. den Toonder, Jaap M. J. Bouten, Carlijn V. C. Stassen, Oscar M. J. A. Sahlgren, Cecilia M. A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions |
title | A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions
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title_full | A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions
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title_fullStr | A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions
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title_full_unstemmed | A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions
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title_short | A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions
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title_sort | biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972738/ https://www.ncbi.nlm.nih.gov/pubmed/29756630 http://dx.doi.org/10.1039/c8lc00286j |
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