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Development of a human primary gut-on-a-chip to model inflammatory processes

Inflammatory bowel disease (IBD) is a complex multi-factorial disease for which physiologically relevant in vitro models are lacking. Existing models are often a compromise between biological relevance and scalability. Here, we integrated intestinal epithelial cells (IEC) derived from human intestin...

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Autores principales: Beaurivage, Claudia, Kanapeckaite, Auste, Loomans, Cindy, Erdmann, Kai S., Stallen, Jan, Janssen, Richard A. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722760/
https://www.ncbi.nlm.nih.gov/pubmed/33293676
http://dx.doi.org/10.1038/s41598-020-78359-2
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author Beaurivage, Claudia
Kanapeckaite, Auste
Loomans, Cindy
Erdmann, Kai S.
Stallen, Jan
Janssen, Richard A. J.
author_facet Beaurivage, Claudia
Kanapeckaite, Auste
Loomans, Cindy
Erdmann, Kai S.
Stallen, Jan
Janssen, Richard A. J.
author_sort Beaurivage, Claudia
collection PubMed
description Inflammatory bowel disease (IBD) is a complex multi-factorial disease for which physiologically relevant in vitro models are lacking. Existing models are often a compromise between biological relevance and scalability. Here, we integrated intestinal epithelial cells (IEC) derived from human intestinal organoids with monocyte-derived macrophages, in a gut-on-a-chip platform to model the human intestine and key aspects of IBD. The microfluidic culture of IEC lead to an increased polarization and differentiation state that closely resembled the expression profile of human colon in vivo. Activation of the model resulted in the polarized secretion of CXCL10, IL-8 and CCL-20 by IEC and could efficiently be prevented by TPCA-1 exposure. Importantly, upregulated gene expression by the inflammatory trigger correlated with dysregulated pathways in IBD patients. Finally, integration of activated macrophages offers a first-step towards a multi-factorial amenable IBD platform that could be scaled up to assess compound efficacy at early stages of drug development or in personalized medicine.
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spelling pubmed-77227602020-12-09 Development of a human primary gut-on-a-chip to model inflammatory processes Beaurivage, Claudia Kanapeckaite, Auste Loomans, Cindy Erdmann, Kai S. Stallen, Jan Janssen, Richard A. J. Sci Rep Article Inflammatory bowel disease (IBD) is a complex multi-factorial disease for which physiologically relevant in vitro models are lacking. Existing models are often a compromise between biological relevance and scalability. Here, we integrated intestinal epithelial cells (IEC) derived from human intestinal organoids with monocyte-derived macrophages, in a gut-on-a-chip platform to model the human intestine and key aspects of IBD. The microfluidic culture of IEC lead to an increased polarization and differentiation state that closely resembled the expression profile of human colon in vivo. Activation of the model resulted in the polarized secretion of CXCL10, IL-8 and CCL-20 by IEC and could efficiently be prevented by TPCA-1 exposure. Importantly, upregulated gene expression by the inflammatory trigger correlated with dysregulated pathways in IBD patients. Finally, integration of activated macrophages offers a first-step towards a multi-factorial amenable IBD platform that could be scaled up to assess compound efficacy at early stages of drug development or in personalized medicine. Nature Publishing Group UK 2020-12-08 /pmc/articles/PMC7722760/ /pubmed/33293676 http://dx.doi.org/10.1038/s41598-020-78359-2 Text en © The Author(s) 2020 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Beaurivage, Claudia
Kanapeckaite, Auste
Loomans, Cindy
Erdmann, Kai S.
Stallen, Jan
Janssen, Richard A. J.
Development of a human primary gut-on-a-chip to model inflammatory processes
title Development of a human primary gut-on-a-chip to model inflammatory processes
title_full Development of a human primary gut-on-a-chip to model inflammatory processes
title_fullStr Development of a human primary gut-on-a-chip to model inflammatory processes
title_full_unstemmed Development of a human primary gut-on-a-chip to model inflammatory processes
title_short Development of a human primary gut-on-a-chip to model inflammatory processes
title_sort development of a human primary gut-on-a-chip to model inflammatory processes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722760/
https://www.ncbi.nlm.nih.gov/pubmed/33293676
http://dx.doi.org/10.1038/s41598-020-78359-2
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