Abstract
In vitro models that better reflect in vivo epithelial barrier (patho-)physiology are urgently required to predict adverse drug effects. Here we introduce extracellular matrix-supported intestinal tubules in perfused microfluidic devices, exhibiting tissue polarization and transporter expression. Forty leak-tight tubules are cultured in parallel on a single plate and their response to pharmacological stimuli is recorded over 125 h using automated imaging techniques. A study comprising 357 gut tubes is performed, of which 93% are leak tight before exposure. EC50-time curves could be extracted that provide insight into both concentration and exposure time response. Full compatibility with standard equipment and user-friendly operation make this Organ-on-a-Chip platform readily applicable in routine laboratories.
Highlights
In vitro models that better reflect in vivo epithelial barrierphysiology are urgently required to predict adverse drug effects
Such conventional Transwell systems are poorly suited for high-resolution kinetic measurements and image-based readouts, and provide only limited information on the underlying mechanisms, leading to barrier disruption. It does not comply with the current paradigm in cell culture that is steadily shifting towards three-dimensional cultures, extracellular matrix (ECM) embedment and addition of perfusion flow[1,2,3,4,5]
Each microfluidic channel structure is comprised of three lanes that are connected to corresponding wells of a microtiter plate that function as inlets and outlets to access the microfluidic culture
Summary
In vitro models that better reflect in vivo epithelial barrier (patho-)physiology are urgently required to predict adverse drug effects. In vitro testing of para-cellular permeability of epithelial barriers is most commonly achieved by cultivating cells on a rigid membrane that separates two medium-containing chambers under static conditions. Such conventional Transwell systems are poorly suited for high-resolution kinetic measurements and image-based readouts, and provide only limited information on the underlying mechanisms, leading to barrier disruption. It does not comply with the current paradigm in cell culture that is steadily shifting towards three-dimensional cultures, extracellular matrix (ECM) embedment and addition of perfusion flow[1,2,3,4,5]. EC50-time curves provide insight in concentration response at increasing exposure time in one single experimental run
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