Human enteroid monolayers as a potential alternative for Ussing chamber and Caco-2 monolayers to study passive permeability and drug efflux

Streekstra, Eva J.; Keuper-Navis, Marit; van den Heuvel, Jeroen J.M.W.; van den Broek, Petra; Stommel, Martijn W.J.; Bervoets, Sander; O'Gorman, Luke; Greupink, Rick; Russel, Frans G.M.; van de Steeg, Evita; de Wildt, Saskia N.

doi:10.1016/j.ejps.2024.106877

European Journal of Pharmaceutical Sciences

2024

DOI: 10.1016/j.ejps.2024.106877

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Human enteroid monolayers as a potential alternative for Ussing chamber and Caco-2 monolayers to study passive permeability and drug efflux

Eva J. Streekstra,

Marit Keuper-Navis,

Jeroen J.M.W. van den Heuvel

et al.

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Intestinal Cells-on-Chip for Permeability Studies

Keuper-Navis,

Eslami Amirabadi,

Donkers

et al. 2024

Micromachines

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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.

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Intestinal Cells-on-Chip for Permeability Studies

Keuper-Navis,

Eslami Amirabadi,

Donkers

et al. 2024

Micromachines

View full text Add to dashboard Cite

show abstract

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Human enteroid monolayers as a potential alternative for Ussing chamber and Caco-2 monolayers to study passive permeability and drug efflux

Cited by 1 publication

References 50 publications

Intestinal Cells-on-Chip for Permeability Studies

Intestinal Cells-on-Chip for Permeability Studies

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