Integrated gut–liver-on-a-chip platform as an in vitro human model of non-alcoholic fatty liver disease
Abstract
Non-alcoholic fatty liver disease (NAFLD) afflicts a large percentage of the population, but no effective treatments have been established so far because of the unsuitability of in vitro assays and experimental models using animals. By co-culturing human gut and liver cell lines interconnected via microfluidics for a closed circulation loop, we created a gut–liver-on-a-chip (iGLC) platform as an in vitro human model of the gut–liver axis (GLA) for the initiation and progression of NAFLD. Microscopic high-content analysis followed by mRNA sequencing showed that co-culturing the gut and liver cells significantly affected each cell type compared to culturing them separately. NAFLD-inducing free fatty acids (FFAs) accumulated in the gut cells and elevated gene expressions associated with retinol metabolism and glucuronidation. The FFA-treated liver cells accumulated intracellular lipid droplets and showed an increase in gene expressions associated with a cellular response to copper ions and endoplasmic reticulum stress. As an in vitro human GLA model, the iGLC platform may serve as an alternative to animal experiments for investigating NAFLD mechanisms.
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Current GLA-MPSs are based on two approaches: the cell-culture insert in microtiter plates and microfluidic devices.
“The current GLA-MPSs are based on two approaches: the cell-culture insert in the microtiter plates 7,11 and microfluidic devices.12,13”
From Gut-liver-axis microphysiological system for studying cellular fluidic shear stress and inter-tissue interaction (2022) · cites this paper as [12]
Use of a microfluidic device allows control of perfusion flow in planar compartmentalized chambers and interconnection of two or more tissue cells via a microfluidic channel with an on-chip micropump.
“In contrast, the use of a microfluidic device allows the control of perfusion flow in the planar compartmentalized chambers and the interconnection of two or more tissue cells via a microfluidic channel with an on-chip micropump.12,13,16”
From Gut-liver-axis microphysiological system for studying cellular fluidic shear stress and inter-tissue interaction (2022) · cites this paper as [12]
The microfluidic device cannot be applied to study organ molecular transport function across the gut barrier because it does not have an apical-to-basal side transport structure such as a porous membrane substrate on the bottom channel.
“Further, the device cannot be applied to study organ molecular transport function across the gut barrier because it does not have an apical to basal side transport structure such as a porous membrane substrate on the bottom channel.12”
From Gut-liver-axis microphysiological system for studying cellular fluidic shear stress and inter-tissue interaction (2022) · cites this paper as [12]
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Cites
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Lipotoxicity and the gut-liver axis in NASH pathogenesis
Marra, F., & Svegliati-Baroni, G. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.11.014 · Cited by 847 · see citing works
Gut-on-a-Chip microenvironment induces human intestinal cells to undergo villus differentiation
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Lipotoxic lethal and sublethal stress signaling in hepatocytes: relevance to NASH pathogenesis
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A guide to the organ-on-a-chip
Leung, C. M., de Haan, P., Ronaldson-Bouchard, K., Kim, G.-A., Ko, J., Rho, H. S., Chen, Z., Habibovic, P., Jeon, N. L., Takayama, S., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00118-6 · Cited by 1,116 · see citing works
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Self-citation
- Authors
- Yang, J., Hirai, Y., Iida, K., Ito, S., Trumm, M., Terada, S., Sakai, R., Tsuchiya, T., Tabata, O., & Kamei, K.-I.
- ORCID
- Publisher
- openRxiv
- Published
- 2020-06-12
- Cited by
- 4
- References
- 6
- Type
- Preprint
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