Intestinal Cells-on-Chip for Permeability Studies

Background: To accurately measure permeability of compounds in the intestine, there is a need for preclinical in vitro models that accurately represent the specificity, integrity and complexity of the human small intestinal barrier. Intestine-on-chip systems hold considerable promise as testing plat...

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Main Authors: Marit Keuper-Navis, Hossein Eslami Amirabadi, Joanne Donkers, Markus Walles, Birk Poller, Bo Heming, Lisanne Pieters, Bjorn de Wagenaar, Adam Myszczyszyn, Theo Sinnige, Bart Spee, Rosalinde Masereeuw, Evita van de Steeg
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Micromachines
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Online Access:https://www.mdpi.com/2072-666X/15/12/1464
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Summary:Background: To accurately measure permeability of compounds in the intestine, there is a need for preclinical in vitro models that accurately represent the specificity, integrity and complexity of the human small intestinal barrier. Intestine-on-chip systems hold considerable promise as testing platforms, but several characteristics still require optimization and further development. Methods: An established intestine-on-chip model for tissue explants was adopted for intestinal cell monolayer culture. A 3D-printed culture disc was designed to allow cell culture in static conditions and subsequent permeability studies in a dynamic environment. Membrane characteristics and standardized read-outs were investigated and compared to traditional permeability studies under static conditions. Results: By starting cultures outside the chip in conventional wells plates, the new cell disc design could support accurate cell monolayer formation for both Caco-2 and human enteroids. When transferred to the chip with laminar flow, there was accurate detection of barrier integrity (FD4 and Cascade Blue) and permeability (atenolol/antipyrine). Both flow and membrane characteristics had a significant impact on permeability outcomes. Conclusions: This novel intestinal cell-on-chip system offers large flexibility for intestinal permeability studies, although it still requires validation with more compounds to reveal its full potential.
ISSN:2072-666X