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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6888156 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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