ArticleScientific reports2016
Functional human induced hepatocytes (hiHeps) with bile acid synthesis and transport capacities: A novel in vitro cholestatic model.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
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- Human iPSC-derived hepatocyte system models cholestasis with tight junction protein 2 deficiency.JHEP reports : innovation in hepatology · 2022Article
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- Prospect ofFrontiers in toxicology · 2021Review
- Dihydro-stilbene gigantol relieves CClActa pharmacologica Sinica · 2020Article
- Stem cell-derived polarized hepatocytes.Nature communications · 2020Article
- Review
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- Optimization of Canalicular ABC Transporter Function in HuH-7 Cells by Modification of Culture Conditions.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- A serum-free medium suitable for maintaining cell morphology and liver-specific function in induced human hepatocytes.Cytotechnology · 2019Article
- Direct cell reprogramming for tissue engineering and regenerative medicine.Journal of biological engineering · 2019Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug-induced cholestasis is a leading cause of drug withdrawal. However, the use of primary human hepatocytes (PHHs), the gold standard for predicting cholestasis in vitro, is limited by their high cost and batch-to-batch variability. Mature hepatocyte characteristics have been observed in human induced hepatocytes (hiHeps) derived from human fibroblast transdifferentiation. Here, we evaluated whether hiHeps could biosynthesize and excrete bile acids (BAs) and their potential as PHH alternatives for cholestasis investigations. Quantitative real-time PCR (qRT-PCR) and western blotting indicated that hiHeps highly expressed BA synthases and functional transporters. Liquid chromatography tandem mass spectrometry (LC-MS/MS) showed that hiHeps produced normal intercellular unconjugated BAs but fewer conjugated BAs than human hepatocytes. When incubated with representative cholestatic agents, hiHeps exhibited sensitive drug-induced bile salt export pump (BSEP) dysfunction, and their response to cholestatic agent-mediated cytotoxicity correlated well with that of PHHs (r
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