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Monday, October 21 • 2:30pm - 3:00pm
Poster Presentation #4- 3D Multicellular Intestine-on-a-chip Model for Disease Modeling and Drug Discovery

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The development of efficient drugs and therapies for treatment of inflammatory bowel disease (IBD) is hampered because of the lack of reliable in vitro and in vivo models. Current models generally fail to recapitulate key aspects of the intestine, resulting in low translatability to the human situation. With the increasing IBD incidence worldwide, there is an unmet need for predictive in vitro models that recapitulate the complex structure of the human intestine. Here, we show the development and characterization of a 3D multicellular perfused intestine-on-a-chip model and its application for investigating and interfering with intestinal inflammation.

Forty independent polarized 3D perfused leak-tight epithelial tubular structures composed of Caco-2 and HT29-MTX-E12 cells were obtained in the microfluidic platform, the OrganoPlate 3-lane. Next, immune competent cells were added to the system and shown to be functional, as demonstrated by the release of cytokines upon activation.

To mimic intestinal inflammation, the model was exposed to tumor necrosis factor (TNF) α and/or interleukin (IL)-1β, whose effects were assessed by measuring the transepithelial electrical resistance (TEER) and secretion of proinflammatory cytokines at the apical and basal sides. The cytokines induced an inflammatory state in the culture, as demonstrated by the impaired barrier integrity and increased IL-8 secretion. We also assessed the applicability of the model in screening anti-inflammatory compounds by using the well-known anti-inflammatory drug TPCA-1. Exposure to the drug prevented an inflammatory state in the model.

Overall, these results suggest that this model provides the versatile modularity of mimicking key features of intestinal inflammation, which positions it at the forefront of high-throughput screening efforts for supporting drug discovery and providing a platform for personalized medicine.

Speakers
LG

Linda Gijzen

Scientist, Mimetas BV
Linda Gijzen, MsC, got her master’s degree in Toxicology and Pathobiology from the Radboud University, the Netherlands, in 2016. Since then she is working as a scientist at the Model Development department at Mimetas, the organ-on-a-chip company, in Leiden. There she is involved... Read More →


Monday October 21, 2019 2:30pm - 3:00pm
Sherry Coutu Seminar Suite Foyer