Non-alcoholic fatty liver disease (NAFLD), characterized by lipid accumulation in the liver,
is the most common cause of liver diseases in Western countries. NAFLD is a major risk factor for
developing hepatocellular carcinoma (HCC); however, in vitro evaluation of hepatic cancerogenesis
fails due to a lack of liver models displaying a proliferation of hepatocytes. Originally designed
to overcome primary human hepatocyte (PHH) shortages, upcyte hepatocytes were engineered
to obtain continuous proliferation and, therefore, could be a suitable tool for HCC research. We
generated upcyte hepatocytes, termed HepaFH3 cells, and compared their metabolic characteristics to
HepG2 hepatoma cells and PHHs isolated from resected livers. For displaying NAFLD-related HCCs,
we induced steatosis in all liver models. Lipid accumulation, lipotoxicity and energy metabolism
were characterized using biochemical assays and Western blot analysis. We showed that proliferating
HepaFH3 cells resemble HepG2, both showing a higher glucose uptake rate, lactate levels and
metabolic rate compared to PHHs. Confluent HepaFH3 cells displayed some similarities to PHHs,
including higher levels of the transaminases AST and ALT compared to proliferating HepaFH3 cells.
We recommend proliferating HepaFH3 cells as a pre-malignant cellular model for HCC research,
while confluent HepaFH3 cells could serve as PHH surrogates for energy metabolism studies.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:88483 |
| Date | 06 December 2023 |
| Creators | Scheffschick, Andrea, Babel, Jonas, Sperling, Sebastian, Nerusch, Julia, Herzog, Natalie, Seehofer, Daniel, Damm, Georg |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2079-7737, 10.3390/biology11081195 |
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