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Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture models

The tumour microenvironment is very complex, and essential in tumour development and drug resistance. The endothelium is critical in the tumour microenvironment: it provides nutrients and oxygen to the tumour and is essential for systemic drug delivery. Therefore, we report a simple, user-friendly m...

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Autores principales: Virumbrales-Muñoz, María, Ayuso, José María, Olave, Marta, Monge, Rosa, de Miguel, Diego, Martínez-Lostao, Luis, Le Gac, Séverine, Doblare, Manuel, Ochoa, Ignacio, Fernandez, Luis J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607255/
https://www.ncbi.nlm.nih.gov/pubmed/28931839
http://dx.doi.org/10.1038/s41598-017-12049-4
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author Virumbrales-Muñoz, María
Ayuso, José María
Olave, Marta
Monge, Rosa
de Miguel, Diego
Martínez-Lostao, Luis
Le Gac, Séverine
Doblare, Manuel
Ochoa, Ignacio
Fernandez, Luis J.
author_facet Virumbrales-Muñoz, María
Ayuso, José María
Olave, Marta
Monge, Rosa
de Miguel, Diego
Martínez-Lostao, Luis
Le Gac, Séverine
Doblare, Manuel
Ochoa, Ignacio
Fernandez, Luis J.
author_sort Virumbrales-Muñoz, María
collection PubMed
description The tumour microenvironment is very complex, and essential in tumour development and drug resistance. The endothelium is critical in the tumour microenvironment: it provides nutrients and oxygen to the tumour and is essential for systemic drug delivery. Therefore, we report a simple, user-friendly microfluidic device for co-culture of a 3D breast tumour model and a 2D endothelium model for cross-talk and drug delivery studies. First, we demonstrated the endothelium was functional, whereas the tumour model exhibited in vivo features, e.g., oxygen gradients and preferential proliferation of cells with better access to nutrients and oxygen. Next, we observed the endothelium structure lost its integrity in the co-culture. Following this, we evaluated two drug formulations of TRAIL (TNF-related apoptosis inducing ligand): soluble and anchored to a LUV (large unilamellar vesicle). Both diffused through the endothelium, LUV-TRAIL being more efficient in killing tumour cells, showing no effect on the integrity of endothelium. Overall, we have developed a simple capillary force-based microfluidic device for 2D and 3D cell co-cultures. Our device allows high-throughput approaches, patterning different cell types and generating gradients without specialised equipment. We anticipate this microfluidic device will facilitate drug screening in a relevant microenvironment thanks to its simple, effective and user-friendly operation.
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spelling pubmed-56072552017-09-24 Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture models Virumbrales-Muñoz, María Ayuso, José María Olave, Marta Monge, Rosa de Miguel, Diego Martínez-Lostao, Luis Le Gac, Séverine Doblare, Manuel Ochoa, Ignacio Fernandez, Luis J. Sci Rep Article The tumour microenvironment is very complex, and essential in tumour development and drug resistance. The endothelium is critical in the tumour microenvironment: it provides nutrients and oxygen to the tumour and is essential for systemic drug delivery. Therefore, we report a simple, user-friendly microfluidic device for co-culture of a 3D breast tumour model and a 2D endothelium model for cross-talk and drug delivery studies. First, we demonstrated the endothelium was functional, whereas the tumour model exhibited in vivo features, e.g., oxygen gradients and preferential proliferation of cells with better access to nutrients and oxygen. Next, we observed the endothelium structure lost its integrity in the co-culture. Following this, we evaluated two drug formulations of TRAIL (TNF-related apoptosis inducing ligand): soluble and anchored to a LUV (large unilamellar vesicle). Both diffused through the endothelium, LUV-TRAIL being more efficient in killing tumour cells, showing no effect on the integrity of endothelium. Overall, we have developed a simple capillary force-based microfluidic device for 2D and 3D cell co-cultures. Our device allows high-throughput approaches, patterning different cell types and generating gradients without specialised equipment. We anticipate this microfluidic device will facilitate drug screening in a relevant microenvironment thanks to its simple, effective and user-friendly operation. Nature Publishing Group UK 2017-09-20 /pmc/articles/PMC5607255/ /pubmed/28931839 http://dx.doi.org/10.1038/s41598-017-12049-4 Text en © The Author(s) 2017 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
Virumbrales-Muñoz, María
Ayuso, José María
Olave, Marta
Monge, Rosa
de Miguel, Diego
Martínez-Lostao, Luis
Le Gac, Séverine
Doblare, Manuel
Ochoa, Ignacio
Fernandez, Luis J.
Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture models
title Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture models
title_full Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture models
title_fullStr Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture models
title_full_unstemmed Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture models
title_short Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture models
title_sort multiwell capillarity-based microfluidic device for the study of 3d tumour tissue-2d endothelium interactions and drug screening in co-culture models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607255/
https://www.ncbi.nlm.nih.gov/pubmed/28931839
http://dx.doi.org/10.1038/s41598-017-12049-4
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