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Image-Assisted Microvessel-on-a-Chip Platform for Studying Cancer Cell Transendothelial Migration Dynamics

With the push to reduce in vivo approaches, the demand for microphysiological models that recapitulate the in vivo settings in vitro is dramatically increasing. Here, we present an extracellular matrix-integrated microfluidic chip with a rounded microvessel of ~100 µm in diameter. Our system display...

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Autores principales: Bertulli, Cristina, Gerigk, Magda, Piano, Nicholas, Liu, Ye, Zhang, Duo, Müller, Thomas, Knowles, Tuomas J., Huang, Yan Yan Shery
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102203/
https://www.ncbi.nlm.nih.gov/pubmed/30127372
http://dx.doi.org/10.1038/s41598-018-30776-0
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author Bertulli, Cristina
Gerigk, Magda
Piano, Nicholas
Liu, Ye
Zhang, Duo
Müller, Thomas
Knowles, Tuomas J.
Huang, Yan Yan Shery
author_facet Bertulli, Cristina
Gerigk, Magda
Piano, Nicholas
Liu, Ye
Zhang, Duo
Müller, Thomas
Knowles, Tuomas J.
Huang, Yan Yan Shery
author_sort Bertulli, Cristina
collection PubMed
description With the push to reduce in vivo approaches, the demand for microphysiological models that recapitulate the in vivo settings in vitro is dramatically increasing. Here, we present an extracellular matrix-integrated microfluidic chip with a rounded microvessel of ~100 µm in diameter. Our system displays favorable characteristics for broad user adaptation: simplified procedure for vessel creation, minimised use of reagents and cells, and the ability to couple live-cell imaging and image analysis to study dynamics of cell-microenvironment interactions in 3D. Using this platform, the dynamic process of single breast cancer cells (LM2-4175) exiting the vessel lumen into the surrounding extracellular matrix was tracked. Here, we show that the presence of endothelial lining significantly reduced the cancer exit events over the 15-hour imaging period: there were either no cancer cells exiting, or the fraction of spontaneous exits was positively correlated with the number of cancer cells in proximity to the endothelial barrier. The capability to map the z-position of individual cancer cells within a 3D vessel lumen enabled us to observe cancer cell transmigration ‘hot spot’ dynamically. We also suggest the variations in the microvessel qualities may lead to the two distinct types of cancer transmigration behaviour. Our findings provide a tractable in vitro model applicable to other areas of microvascular research.
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spelling pubmed-61022032018-08-27 Image-Assisted Microvessel-on-a-Chip Platform for Studying Cancer Cell Transendothelial Migration Dynamics Bertulli, Cristina Gerigk, Magda Piano, Nicholas Liu, Ye Zhang, Duo Müller, Thomas Knowles, Tuomas J. Huang, Yan Yan Shery Sci Rep Article With the push to reduce in vivo approaches, the demand for microphysiological models that recapitulate the in vivo settings in vitro is dramatically increasing. Here, we present an extracellular matrix-integrated microfluidic chip with a rounded microvessel of ~100 µm in diameter. Our system displays favorable characteristics for broad user adaptation: simplified procedure for vessel creation, minimised use of reagents and cells, and the ability to couple live-cell imaging and image analysis to study dynamics of cell-microenvironment interactions in 3D. Using this platform, the dynamic process of single breast cancer cells (LM2-4175) exiting the vessel lumen into the surrounding extracellular matrix was tracked. Here, we show that the presence of endothelial lining significantly reduced the cancer exit events over the 15-hour imaging period: there were either no cancer cells exiting, or the fraction of spontaneous exits was positively correlated with the number of cancer cells in proximity to the endothelial barrier. The capability to map the z-position of individual cancer cells within a 3D vessel lumen enabled us to observe cancer cell transmigration ‘hot spot’ dynamically. We also suggest the variations in the microvessel qualities may lead to the two distinct types of cancer transmigration behaviour. Our findings provide a tractable in vitro model applicable to other areas of microvascular research. Nature Publishing Group UK 2018-08-20 /pmc/articles/PMC6102203/ /pubmed/30127372 http://dx.doi.org/10.1038/s41598-018-30776-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Bertulli, Cristina
Gerigk, Magda
Piano, Nicholas
Liu, Ye
Zhang, Duo
Müller, Thomas
Knowles, Tuomas J.
Huang, Yan Yan Shery
Image-Assisted Microvessel-on-a-Chip Platform for Studying Cancer Cell Transendothelial Migration Dynamics
title Image-Assisted Microvessel-on-a-Chip Platform for Studying Cancer Cell Transendothelial Migration Dynamics
title_full Image-Assisted Microvessel-on-a-Chip Platform for Studying Cancer Cell Transendothelial Migration Dynamics
title_fullStr Image-Assisted Microvessel-on-a-Chip Platform for Studying Cancer Cell Transendothelial Migration Dynamics
title_full_unstemmed Image-Assisted Microvessel-on-a-Chip Platform for Studying Cancer Cell Transendothelial Migration Dynamics
title_short Image-Assisted Microvessel-on-a-Chip Platform for Studying Cancer Cell Transendothelial Migration Dynamics
title_sort image-assisted microvessel-on-a-chip platform for studying cancer cell transendothelial migration dynamics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102203/
https://www.ncbi.nlm.nih.gov/pubmed/30127372
http://dx.doi.org/10.1038/s41598-018-30776-0
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