In vitro demonstration of intestinal absorption mechanisms of different sugars using 3D organotypic tissues in a fluidic device

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Alessandra Marrella
Paolo Buratti
Jan Markus
Giuseppe Firpo
Mario Pesenti
Tim Landry
Seyoum Ayehunie
Silvia Scaglione
Helena Kandarova
Maurizio Aiello

Abstract

Intestinal permeability is crucial in regulating the bioavailability and consecutively the biological effects of drugs and compounds. However, systematic and quantitative studies of absorption of molecules are quite limited due to the lack of reliable experimental models able to mimic in vivo responses. In this work, we present a novel platform as in vitro fluidic model of healthy and pathological small intestinal barrier using 3D reconstructed intestinal epithelium integrated with a fluid-dynamic bioreactor resembling the physiological stimuli of the intestinal environment (MIVO®). The platform has been investigated, both in healthy and induced pathological conditions, by monitoring the absorption of two non-metabolized sugars, lactulose and mannitol, frequently used as indicators of intestinal barrier dysfunctions. The results showed that an in vivo-like plateau of the percentage of absorbed sugars was reached for lactulose and mannitol and that the mannitol absorbed was much greater than the lactulose, in line with clinical data, thus revealing the good reliability of the model. Moreover, a model of altered intestinal permeability has been generated by depleting extracellular Ca2+ using calcium specific chelator. Interestingly, after calcium depletion treatment, the pattern of sugar passage comparable with the healthy tissue was completely restored only in dynamic conditions within MIVO® chamber, due to the beneficial role of the dynamic fluid flow beneath the membrane. Therefore, the MIVO® combined with EpiIntestinalTM™ platform can represent a reliable in vitro model of healthy and pathological small intestinal barrier to study the passage of molecules, by discriminating the two main intestinal absorption mechanisms.

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How to Cite
Marrella, A., Buratti, P., Markus, J., Firpo, G., Pesenti, M., Landry, T., Ayehunie, S., Scaglione, S., Kandarova, H. and Aiello, M. (2019) “In vitro demonstration of intestinal absorption mechanisms of different sugars using 3D organotypic tissues in a fluidic device”, ALTEX - Alternatives to animal experimentation. doi: 10.14573/altex.1908311.
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