ArticleScientific reports2016
Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease.
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 328 papers.
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Who cites it
328 citing papers in PubMed, 690 citations in OpenAlex.
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- Reverse bioengineering of the liver: developmental principles for next-generation liver-on-a-chip systems.Communications biology · 2026Review
- Trephine Stoma in High-Risk Patients: Feasibility and Short-Term Outcomes.Journal of clinical medicine · 2026Article
- Assessing drug-induced liver injury liabilities in human and animal hepatocytes under static and perfused spheroid culture conditions.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Free Fatty acid-induced disruption of hepatic vitamin D metabolism impairs bone homeostasis in an in vitro 3D human liver-bone model.Archives of toxicology · 2026Article
- The effect of rocking speed and cell inoculation density on hepatic spheroid size: A simple method for size modulation.Bioengineering & translational medicine · 2026Article
- The making of cells and organs in xenogeneic animal bioreactor.Signal transduction and targeted therapy · 2026Review
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- Exposure Duration Shapes the Hepatic Response to GenX: Divergent Acute and Chronic Transcriptomic Profiles Reveal Non-Monotonic Dose Effects and Increased Sensitivity in Human Liver Spheroids.bioRxiv : the preprint server for biology · 2026Article
- Mechanistically resolved prediction of compound hepatotoxicity using primary human liver spheroids-Application to recent real-world cases.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- 3D Liver Fibrosis Models in Lab: A Novel Modality for Drug Screening.Pharmacology research & perspectives · 2026Review
- Automation of 3D liver spheroid generation and acetaminophen dose-response on the MO:BOT enhances assay robustness and precision.Scientific reports · 2026Article
- Cell line identity rather than medium composition determines transcriptomic profiles of HepaRG and HuH7 cells cultured in chemically defined or serum-based media: comparison with primary human hepatocytes.Archives of toxicology · 2026Article
- A Machine Vision-Guided Microphysiological Platform With Automated Microfluidics Enables Longitudinal Biomarker Monitoring and Emulation of Translationally Relevant Exposure Scenarios.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
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- Biobanked Liver Organoids: A Roadmap for Precision Hepatology.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Hepatocyte Models for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comparative Analysis of Non-HepG2 Cell Models.International journal of molecular sciences · 2026Review
- Measuring Propidium Iodide Brightness as a Function of Viability: A High-Throughput Quantitative Assessment of Hepatic Spheroids.Artificial organs · 2026Article
- Single-cell transcriptomics of acetaminophen-induced responses in human 2D and 3D liver microtissues.Archives of toxicology · 2026Article
268 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver biology and function, drug-induced liver injury (DILI) and liver diseases are difficult to study using current in vitro models such as primary human hepatocyte (PHH) monolayer cultures, as their rapid de-differentiation restricts their usefulness substantially. Thus, we have developed and extensively characterized an easily scalable 3D PHH spheroid system in chemically-defined, serum-free conditions. Using whole proteome analyses, we found that PHH spheroids cultured this way were similar to the liver in vivo and even retained their inter-individual variability. Furthermore, PHH spheroids remained phenotypically stable and retained morphology, viability, and hepatocyte-specific functions for culture periods of at least 5 weeks. We show that under chronic exposure, the sensitivity of the hepatocytes drastically increased and toxicity of a set of hepatotoxins was detected at clinically relevant concentrations. An interesting example was the chronic toxicity of fialuridine for which hepatotoxicity was mimicked after repeated-dosing in the PHH spheroid model, not possible to detect using previous in vitro systems. Additionally, we provide proof-of-principle that PHH spheroids can reflect liver pathologies such as cholestasis, steatosis and viral hepatitis. Combined, our results demonstrate that the PHH spheroid system presented here constitutes a versatile and promising in vitro system to study liver function, liver diseases, drug targets and long-term DILI.
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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.