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Development of a Gut-on-a-Chip Model for High Throughput Disease Modeling and Drug Discovery

A common bottleneck in any drug development process is finding sufficiently accurate models that capture key aspects of disease development and progression. Conventional drug screening models often rely on simple 2D culture systems that fail to recapitulate the complexity of the organ situation. In...

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Autores principales: Beaurivage, Claudia, Naumovska, Elena, Chang, Yee Xiang, Elstak, Edo D., Nicolas, Arnaud, Wouters, Heidi, van Moolenbroek, Guido, Lanz, Henriëtte L., Trietsch, Sebastiaan J., Joore, Jos, Vulto, Paul, Janssen, Richard A.J., Erdmann, Kai S., Stallen, Jan, Kurek, Dorota
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888156/
https://www.ncbi.nlm.nih.gov/pubmed/31726729
http://dx.doi.org/10.3390/ijms20225661
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author Beaurivage, Claudia
Naumovska, Elena
Chang, Yee Xiang
Elstak, Edo D.
Nicolas, Arnaud
Wouters, Heidi
van Moolenbroek, Guido
Lanz, Henriëtte L.
Trietsch, Sebastiaan J.
Joore, Jos
Vulto, Paul
Janssen, Richard A.J.
Erdmann, Kai S.
Stallen, Jan
Kurek, Dorota
author_facet Beaurivage, Claudia
Naumovska, Elena
Chang, Yee Xiang
Elstak, Edo D.
Nicolas, Arnaud
Wouters, Heidi
van Moolenbroek, Guido
Lanz, Henriëtte L.
Trietsch, Sebastiaan J.
Joore, Jos
Vulto, Paul
Janssen, Richard A.J.
Erdmann, Kai S.
Stallen, Jan
Kurek, Dorota
author_sort Beaurivage, Claudia
collection PubMed
description A common bottleneck in any drug development process is finding sufficiently accurate models that capture key aspects of disease development and progression. Conventional drug screening models often rely on simple 2D culture systems that fail to recapitulate the complexity of the organ situation. In this study, we show the application of a robust high throughput 3D gut-on-a-chip model for investigating hallmarks of inflammatory bowel disease (IBD). Using the OrganoPlate platform, we subjected enterocyte-like cells to an immune-relevant inflammatory trigger in order to recapitulate key events of IBD and to further investigate the suitability of this model for compound discovery and target validation activities. The induction of inflammatory conditions caused a loss of barrier function of the intestinal epithelium and its activation by increased cytokine production, two events observed in IBD physiopathology. More importantly, anti-inflammatory compound exposure prevented the loss of barrier function and the increased cytokine release. Furthermore, knockdown of key inflammatory regulators RELA and MYD88 through on-chip adenoviral shRNA transduction alleviated IBD phenotype by decreasing cytokine production. In summary, we demonstrate the routine use of a gut-on-a-chip platform for disease-specific aspects modeling. The approach can be used for larger scale disease modeling, target validation and drug discovery purposes.
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spelling pubmed-68881562019-12-09 Development of a Gut-on-a-Chip Model for High Throughput Disease Modeling and Drug Discovery Beaurivage, Claudia Naumovska, Elena Chang, Yee Xiang Elstak, Edo D. Nicolas, Arnaud Wouters, Heidi van Moolenbroek, Guido Lanz, Henriëtte L. Trietsch, Sebastiaan J. Joore, Jos Vulto, Paul Janssen, Richard A.J. Erdmann, Kai S. Stallen, Jan Kurek, Dorota Int J Mol Sci Article A common bottleneck in any drug development process is finding sufficiently accurate models that capture key aspects of disease development and progression. Conventional drug screening models often rely on simple 2D culture systems that fail to recapitulate the complexity of the organ situation. In this study, we show the application of a robust high throughput 3D gut-on-a-chip model for investigating hallmarks of inflammatory bowel disease (IBD). Using the OrganoPlate platform, we subjected enterocyte-like cells to an immune-relevant inflammatory trigger in order to recapitulate key events of IBD and to further investigate the suitability of this model for compound discovery and target validation activities. The induction of inflammatory conditions caused a loss of barrier function of the intestinal epithelium and its activation by increased cytokine production, two events observed in IBD physiopathology. More importantly, anti-inflammatory compound exposure prevented the loss of barrier function and the increased cytokine release. Furthermore, knockdown of key inflammatory regulators RELA and MYD88 through on-chip adenoviral shRNA transduction alleviated IBD phenotype by decreasing cytokine production. In summary, we demonstrate the routine use of a gut-on-a-chip platform for disease-specific aspects modeling. The approach can be used for larger scale disease modeling, target validation and drug discovery purposes. MDPI 2019-11-12 /pmc/articles/PMC6888156/ /pubmed/31726729 http://dx.doi.org/10.3390/ijms20225661 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Beaurivage, Claudia
Naumovska, Elena
Chang, Yee Xiang
Elstak, Edo D.
Nicolas, Arnaud
Wouters, Heidi
van Moolenbroek, Guido
Lanz, Henriëtte L.
Trietsch, Sebastiaan J.
Joore, Jos
Vulto, Paul
Janssen, Richard A.J.
Erdmann, Kai S.
Stallen, Jan
Kurek, Dorota
Development of a Gut-on-a-Chip Model for High Throughput Disease Modeling and Drug Discovery
title Development of a Gut-on-a-Chip Model for High Throughput Disease Modeling and Drug Discovery
title_full Development of a Gut-on-a-Chip Model for High Throughput Disease Modeling and Drug Discovery
title_fullStr Development of a Gut-on-a-Chip Model for High Throughput Disease Modeling and Drug Discovery
title_full_unstemmed Development of a Gut-on-a-Chip Model for High Throughput Disease Modeling and Drug Discovery
title_short Development of a Gut-on-a-Chip Model for High Throughput Disease Modeling and Drug Discovery
title_sort development of a gut-on-a-chip model for high throughput disease modeling and drug discovery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888156/
https://www.ncbi.nlm.nih.gov/pubmed/31726729
http://dx.doi.org/10.3390/ijms20225661
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