Scheffschick, Andrea
[Author];
Babel, Jonas
[Author];
Sperling, Sebastian
[Author];
Nerusch, Julia
[Author];
Herzog, Natalie
[Author];
Seehofer, Daniel
[Author];
Damm, Georg
[Author]
Primary-like Human Hepatocytes Genetically Engineered to Obtain Proliferation Competence as a Capable Application for Energy Metabolism Experiments in In Vitro Oncologic Liver Models
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Media type:
E-Article
Title:
Primary-like Human Hepatocytes Genetically Engineered to Obtain Proliferation Competence as a Capable Application for Energy Metabolism Experiments in In Vitro Oncologic Liver Models
Contributor:
Scheffschick, Andrea
[Author];
Babel, Jonas
[Author];
Sperling, Sebastian
[Author];
Nerusch, Julia
[Author];
Herzog, Natalie
[Author];
Seehofer, Daniel
[Author];
Damm, Georg
[Author]
Description:
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 fordeveloping hepatocellular carcinoma (HCC); however, in vitro evaluation of hepatic cancerogenesisfails due to a lack of liver models displaying a proliferation of hepatocytes. Originally designedto overcome primary human hepatocyte (PHH) shortages, upcyte hepatocytes were engineeredto obtain continuous proliferation and, therefore, could be a suitable tool for HCC research. Wegenerated upcyte hepatocytes, termed HepaFH3 cells, and compared their metabolic characteristics toHepG2 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 metabolismwere characterized using biochemical assays and Western blot analysis. We showed that proliferatingHepaFH3 cells resemble HepG2, both showing a higher glucose uptake rate, lactate levels andmetabolic 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.