Developing in vitro assays to transform gastrointestinal safety assessment: potential for microphysiological systems.

Lab on a Chip
Matthew F PetersKyle L Kolaja

Abstract

Drug-induced gastrointestinal toxicities (DI-GITs) are among the most common adverse events in clinical trials. High prevalence of DI-GIT has persisted among new drugs due in part to the lack of robust experimental tools to allow early detection or to guide optimization of safer molecules. Developing in vitro assays for the leading GI toxicities (nausea, vomiting, diarrhoea, constipation, and abdominal pain) will likely involve recapitulating complex physiological properties that require contributions from diverse cell/tissue types including epithelial, immune, microbiome, nerve, and muscle. While this stipulation may be beyond traditional 2D monocultures of intestinal cell lines, emerging 3D GI microtissues capture interactions between diverse cell and tissue types. These interactions give rise to microphysiologies fundamental to gut biology. For GI microtissues, organoid technology was the breakthrough that introduced intestinal stem cells with the capability of differentiating into each of the epithelial cell types and that self-organize into a multi-cellular tissue proxy with villus- and crypt-like domains. Recently, GI microtissues generated using miniaturized devices with microfluidic flow and cyclic peristaltic strain we...Continue Reading

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Citations

Sep 12, 2020·Nature Reviews. Drug Discovery·Lucie A LowDanilo A Tagle
Jul 18, 2020·International Journal of Molecular Sciences·Elena NaumovskaDorota Kurek
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Apr 27, 2021·Experimental Biology and Medicine·Passley Hargrove-GrimesDanilo A Tagle

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Methods Mentioned

BETA
biopsies
gene knockout
biopsy

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