Abstract
The intestine is a complex organ formed of different types of cell distributed in different layers of tissue. To minimize animal experiments, for decades, researchers have been trying to develop in vitro/ex vivo systems able to mimic the cellular diversity naturally found in the gut. Such models not only help our understanding of the gut physiology but also of intestinal toxicity. This review describes the different systems used to evaluate the effects of drugs/contaminants on intestinal functions and compares their advantages and limitations. The comparison showed that the organotypic model is the best available model to perform intestinal toxicity studies, including on human tissues.
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Acknowledgements
This research was partially supported by the French National Research Agency (projects CaDON ANR-15-CE21-0001, Fumolip ANR-16-CE21-0003, and ExpoMycoPig17-CARN-012-001). The authors thank D. Goodfellow for English editing.
Model | Advantages | Limitations |
|---|---|---|
Primary cells | - Close to reality - Simple model enable easier identification of molecular events involved in toxicity | - Isolation of primary human cells requires access to human tissue - Short lifespan limits their use to very short-term studies - Lack of standardization |
Immortalized cells | - Can be maintained for a long time in culture (allowing long-term exposure experiments) - Simple model enabling easier identification of molecular events involved in toxic mechanisms - Low variability of results obtained with this model | - Not all cell types present in the epithelium can be isolated and cultured - Immortalized cells are transformed |
Tumor cell lines | - Commercially available - Can be maintained for a long time in culture (allowing long-term exposure experiments) - Enable separate evaluation of the effects of toxins on major cell types present in the epithelium when co-cultured (e.g. enterocytes and goblet cells) | - Display genetic alterations - Far from the physiological state |
Explants | - Contain all cell types normally present in the epithelium, in the correct proportions - May also contain other cells types such as immune cells, myofibroblasts, and cells from the enteric nerve system (ENS) (neurons and enteric glial cells) | - Limited survival time (48 h) - Access to apical compartment only when mounted in a Ussing chamber - Require access to human intestinal tissue - Higher variability due to inter-individual differences in response to toxins |
Organoids | - Contain most of the cell types normally present in the epithelium (but with no guarantee of them being in the correct proportion) - Can be maintained for a long time in culture, allowing long-term exposure to toxins - Commercially available (low variability) - Derived from healthy or diseased individuals | - Contain only epithelial cells (absence of immune or ENS cells except if co-cultured with other cells) |
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Maresca, M., Pinton, P., Ajandouz, E.H., Menard, S., Ferrier, L., Oswald, I.P. (2018). Overview and Comparison of Intestinal Organotypic Models, Intestinal Cells, and Intestinal Explants Used for Toxicity Studies. In: Bagnoli, F., Rappuoli, R. (eds) Three Dimensional Human Organotypic Models for Biomedical Research. Current Topics in Microbiology and Immunology, vol 430. Springer, Cham. https://doi.org/10.1007/82_2018_142
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