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Open AccessArticle

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

1
Galapagos BV, Zernikedreef 16, 2333 CL Leiden, The Netherlands
2
Department of Biomedical Sciences, University of Sheffield, Western Bank, Sheffield S10 2TN, UK
3
Mimetas BV, J.H. Oortweg 16, 2333 CH Leiden, The Netherlands
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(22), 5661; https://doi.org/10.3390/ijms20225661
Received: 3 October 2019 / Revised: 7 November 2019 / Accepted: 8 November 2019 / Published: 12 November 2019
(This article belongs to the Section Molecular Pharmacology)
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. View Full-Text
Keywords: inflammation; inflammatory bowel disease; gut-on-a-chip; Organ-on-a-Chip; microfluidic; drug discovery; disease modeling inflammation; inflammatory bowel disease; gut-on-a-chip; Organ-on-a-Chip; microfluidic; drug discovery; disease modeling
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Beaurivage, C.; Naumovska, E.; Chang, Y.X.; Elstak, E.D.; Nicolas, A.; Wouters, H.; van Moolenbroek, G.; Lanz, H.L.; Trietsch, S.J.; Joore, J.; Vulto, P.; Janssen, R.A.; Erdmann, K.S.; Stallen, J.; Kurek, D. Development of a Gut-on-a-Chip Model for High Throughput Disease Modeling and Drug Discovery. Int. J. Mol. Sci. 2019, 20, 5661.

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