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

Abstract 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...

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Autores principales:	Claudia Beaurivage, Auste Kanapeckaite, Cindy Loomans, Kai S. Erdmann, Jan Stallen, Richard A. J. Janssen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5ee09f4d5dd6420bbe0cfc533c9d9934
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spelling	oai:doaj.org-article:5ee09f4d5dd6420bbe0cfc533c9d99342021-12-02T12:33:05ZDevelopment of a human primary gut-on-a-chip to model inflammatory processes10.1038/s41598-020-78359-22045-2322https://doaj.org/article/5ee09f4d5dd6420bbe0cfc533c9d99342020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78359-2https://doaj.org/toc/2045-2322Abstract 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.Claudia BeaurivageAuste KanapeckaiteCindy LoomansKai S. ErdmannJan StallenRichard A. J. JanssenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-16 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claudia Beaurivage Auste Kanapeckaite Cindy Loomans Kai S. Erdmann Jan Stallen Richard A. J. Janssen Development of a human primary gut-on-a-chip to model inflammatory processes
description	Abstract 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.
format	article
author	Claudia Beaurivage Auste Kanapeckaite Cindy Loomans Kai S. Erdmann Jan Stallen Richard A. J. Janssen
author_facet	Claudia Beaurivage Auste Kanapeckaite Cindy Loomans Kai S. Erdmann Jan Stallen Richard A. J. Janssen
author_sort	Claudia Beaurivage
title	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_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_sort	development of a human primary gut-on-a-chip to model inflammatory processes
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/5ee09f4d5dd6420bbe0cfc533c9d9934
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Development of a human primary gut-on-a-chip to model inflammatory processes

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