ArticleJournal of hepatology2015
Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes.
Article in Journal of hepatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 2 of them syntheses that pooled it.
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Who cites it
189 citing papers in PubMed, 2 syntheses or guidelines pooled it, 338 citations in OpenAlex.
- A comprehensive transcriptomic comparison of hepatocyte model systems improves selection of models for experimental use.Communications biology · 2022Pooled it
- Engineered tissues and strategies to overcome challenges in drug development.Advanced drug delivery reviews · 2020Pooled it
- Transient culture of adult human hepatocytes as organoids improves engineered liver engraftment.Biomaterials · 2027Article
- Hepatitis B virus protein X promotes survival and loss of hepatocyte identity in a differentiated human liver organoid system.Cell death and differentiation · 2026Article
- Reverse bioengineering of the liver: developmental principles for next-generation liver-on-a-chip systems.Communications biology · 2026Review
- Three-dimensional organoid culture enhances functional maturation of human pluripotent stem cell-derived hepatocytes.Molecular biology reports · 2026Article
- Article
- A CYP3A7 metabolically competent human induced pluripotent stem cell-derived hepatocyte-like cell (hHLCDrug metabolism and disposition: the biological fate of chemicals · 2026Article
- Article
- Transcriptomic Profile of Directed Differentiation of iPSCs into Hepatocyte-like Cells.International journal of molecular sciences · 2026Article
- Effect of 2D and 3D ECM and Biomechanical Cues on Human iPSC-Derived Liver Progenitor Cell Differentiation.Advanced healthcare materials · 2026Article
- Therapeutic priming of liver regeneration: from mechanisms toFrontiers in transplantation · 2026Review
- Primary Human Tissue Models for Metabolic Dysfunction-Associated Liver Disease - toward Streamlining Drug Discovery with Patient-Derived Assays.Advanced biology · 2025Review
- Expansion of human hepatocytes and their application in three-dimensional culture and genetic manipulation.Nature protocols · 2025Article
- Novel emerging cell and organoid systems for the study of drug metabolism and toxicity in humans.Drug metabolism and disposition: the biological fate of chemicals · 2025Review
- Advances in Cytotoxicity Testing: From In Vitro Assays to In Silico Models.International journal of molecular sciences · 2025Review
- Application of Induced Pluripotent Stem Cells (iPSCs) in Hereditary and Viral Diseases of the Liver: Modeling and Treatment.International journal of molecular sciences · 2025Review
- In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025Review
- Enhancement of hepatic differentiation from induced pluripotent stem cells by suppressing epithelial-mesenchymal transition.Hepatology communications · 2025Article
- Functional Liver Cell-Based Platforms in Biomedical Research.Pharmacology research & perspectives · 2025Review
129 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsHepatocyte-like cells (HLCs), differentiated from pluripotent stem cells by the use of soluble factors, can model human liver function and toxicity. However, at present HLC maturity and whether any deficit represents a true fetal state or aberrant differentiation is unclear and compounded by comparison to potentially deteriorated adult hepatocytes. Therefore, we generated HLCs from multiple lineages, using two different protocols, for direct comparison with fresh fetal and adult hepatocytes.
methodsProtocols were developed for robust differentiation. Multiple transcript, protein and functional analyses compared HLCs to fresh human fetal and adult hepatocytes.
resultsHLCs were comparable to those of other laboratories by multiple parameters. Transcriptional changes during differentiation mimicked human embryogenesis and showed more similarity to pericentral than periportal hepatocytes. Unbiased proteomics demonstrated greater proximity to liver than 30 other human organs or tissues. However, by comparison to fresh material, HLC maturity was proven by transcript, protein and function to be fetal-like and short of the adult phenotype. The expression of 81% phase 1 enzymes in HLCs was significantly upregulated and half were statistically not different from fetal hepatocytes. HLCs secreted albumin and metabolized testosterone (CYP3A) and dextrorphan (CYP2D6) like fetal hepatocytes. In seven bespoke tests, devised by principal components analysis to distinguish fetal from adult hepatocytes, HLCs from two different source laboratories consistently demonstrated fetal characteristics.
conclusionsHLCs from different sources are broadly comparable with unbiased proteomic evidence for faithful differentiation down the liver lineage. This current phenotype mimics human fetal rather than adult hepatocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.