A model of hepatic steatosis with declined viability and function in a liver-organ-on-a-chip
Issued Date
2023-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85173633121
Journal Title
Scientific Reports
Volume
13
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.13 No.1 (2023)
Suggested Citation
Wiriyakulsit N., Keawsomnuk P., Thongin S., Ketsawatsomkron P., Muta K. A model of hepatic steatosis with declined viability and function in a liver-organ-on-a-chip. Scientific Reports Vol.13 No.1 (2023). doi:10.1038/s41598-023-44198-0 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/90674
Title
A model of hepatic steatosis with declined viability and function in a liver-organ-on-a-chip
Author's Affiliation
Other Contributor(s)
Abstract
Nonalcoholic fatty liver disease (NAFLD) begins with benign steatosis caused by ectopic storage of triacylglycerols in the liver. Persistent steatosis, in combination with other genetic and environmental factors, leads to nonalcoholic steatohepatitis (NASH) characterized by functional impairment, inflammation, and fibrosis. However, it remains unclear how persistent steatosis directly contributes to the progression of NAFLD, which may represent a therapeutic target. The organ-on-a-chip (OOC) has emerged as a new culture platform to recapitulate human pathological conditions under which drug candidates can be screened. Here, we developed a simple OOC steatosis model using the Mimetas OrganoPlate with a human liver cell line, HepG2. Treating the HepG2 OOCs with fatty acid overload induced steatosis within 24 h. Moreover, persistent steatosis for 6 days impaired OOC viability and hepatic function, as measured by a WST-8 assay and albumin production, respectively. Lastly, the HepG2 OOCs were exposed to drugs being tested in clinical trials for NAFLD/NASH during the 6-day period. Pioglitazone improved the OOC viability while elafibranor reduced the steatosis in association with reduced viability and albumin production. In conclusion, we show that the HepG2 steatosis OOC model is a useful tool on which the efficacy and toxicity of various therapeutic candidates can be tested.