Abstract
The interaction between the gut and the liver, often known as the gut-liver axis, play crucial roles in modulating the body’s responses to the xenobiotics as well as progression of diseases. Dysfunction of the axis can cause metabolic disorders as well as obesity, diabetes, and fatty liver disease. During the progression of such diseases, inflammatory responses involving the immune system also play an important part. In this study, we developed a three-tissue microphysiological system (MPS) that can accommodate three different cell types in separated compartments connected via fluidic channels in a microfluidic device. Using computational fluid dynamics, geometry of fluidic channels and flow conditions were optimized for seeding and culturing different cell types in the three-tissue MPS. Caco-2 (gut), RAW264.7 (immune), and HepG2 (liver) cells were seeded and cultured in the chip. Stimulation of the gut cells in the MPS with lipopolysaccharide (LPS) resulted in induction of inflammatory response and production of nitric oxide (NO) in all connected chambers. The anti-inflammatory effect of luteolin was demonstrated. Our study demonstrates that the three-tissue MPS can recapitulate the inflammatory responses involving the gut, liver and immune cells.
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Acknowledgments
This work was supported by National Research Foundation of Korea (Basic Research Lab, 2019R1A4A1025958), and Hongik University Research Fund. This work was also supported by the Technology Innovation Program funded by the Ministry of Trade, Industry & Energy (MOTIE), Republic of Korea (20008414, Development of intestine-liver-kidney multiorgan tissue chip mimicking absorption distribution metabolism excretion of drug), Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2018R1A6A1A03024231), the Ministry of Science and ICT (MSIT) (2018R1C1B5085757).
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Jeon, Jw., Choi, N., Lee, S.H. et al. Three-tissue microphysiological system for studying inflammatory responses in gut-liver Axis. Biomed Microdevices 22, 65 (2020). https://doi.org/10.1007/s10544-020-00519-y
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DOI: https://doi.org/10.1007/s10544-020-00519-y