ArticleGastroenterology2021
High-Fidelity Drug-Induced Liver Injury Screen Using Human Pluripotent Stem Cell-Derived Organoids.
Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 194 papers, 1 of them a synthesis that pooled it.
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Who cites it
194 citing papers in PubMed, 1 synthesis or guideline pooled it, 340 citations in OpenAlex.
- Liver organoids: From fabrication to application in liver diseases.Frontiers in physiology · 2022Pooled it
- An oral, liver-restricted LXR inverse agonist for dyslipidemia: preclinical development and phase 1 trial.Nature medicine · 2026Trial
- High-Throughput Morphological Profiling of Patient-Derived Human Liver Organoids for Hepatotoxicity Hazard Identification and Compound Prioritization.bioRxiv : the preprint server for biology · 2026Article
- Reverse bioengineering of the liver: developmental principles for next-generation liver-on-a-chip systems.Communications biology · 2026Review
- The transformative impact of stem cell core facilities in biomedical research.Stem cell reports · 2026Review
- Induced pluripotent stem cells from discovery to translation.Nature medicine · 2026Review
- In Vitro Three-Dimensional Human Liver Model for Drug-Induced Liver and Bile Duct Injury Prediction.Toxics · 2026Article
- Next-Generation Hepatocyte Expansion: Bridging Molecular Reprogramming with Multicellular Organoids for Clinical Translation.Stem cell reviews and reports · 2026Review
- Automation of 3D liver spheroid generation and acetaminophen dose-response on the MO:BOT enhances assay robustness and precision.Scientific reports · 2026Article
- Multiple organ dysfunction syndrome: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Human organoids: Fit for drug discovery?Stem cell reports · 2026Review
- Lessons on multicellular two- (2D) and three-dimensional (3D) culture in parasitology: Insights, challenges and future directions.International journal for parasitology · 2026Review
- Biobanked Liver Organoids: A Roadmap for Precision Hepatology.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Translating Pharmacology from Animal Models to Organoids: Advancing Predictive Human Biology in Drug Discovery.Stem cell reviews and reports · 2026Review
- Automated and scalable expansion of human liver organoids for translational applications.Journal of translational medicine · 2026Article
- Reimagining human-centric drug development with new approach methodologies.Science (New York, N.Y.) · 2026Review
- New approach methodologies to model liver fibrosis in metabolic dysfunction-associated steatohepatitis.BMB reports · 2026Review
- [Advances in the construction and application of a novel liver organoid model for hepatitis B virus infection].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Article
- Organoids in drug development: from predictive models to regulatory integration.Drug discovery today · 2026Review
134 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsPreclinical identification of compounds at risk of causing drug induced liver injury (DILI) remains a significant challenge in drug development, highlighting a need for a predictive human system to study complicated DILI mechanism and susceptibility to individual drug. Here, we established a human liver organoid (HLO)-based screening model for analyzing DILI pathology at organoid resolution.
methodsWe first developed a reproducible method to generate HLO from storable foregut progenitors from pluripotent stem cell (PSC) lines with reproducible bile transport function. The qRT-PCR and single cell RNA-seq determined hepatocyte transcriptomic state in cells of HLO relative to primary hepatocytes. Histological and ultrastructural analyses were performed to evaluate micro-anatomical architecture. HLO based drug-induced liver injury assays were transformed into a 384 well based high-speed live imaging platform.
resultsHLO, generated from 10 different pluripotent stem cell lines, contain polarized immature hepatocytes with bile canaliculi-like architecture, establishing the unidirectional bile acid transport pathway. Single cell RNA-seq profiling identified diverse and zonal hepatocytic populations that in part emulate primary adult hepatocytes. The accumulation of fluorescent bile acid into organoid was impaired by CRISPR-Cas9-based gene editing and transporter inhibitor treatment with BSEP. Furthermore, we successfully developed an organoid based assay with multiplexed readouts measuring viability, cholestatic and/or mitochondrial toxicity with high predictive values for 238 marketed drugs at 4 different concentrations (Sensitivity: 88.7%, Specificity: 88.9%). LoT positively predicts genomic predisposition (CYP2C9∗2) for Bosentan-induced cholestasis.
conclusionsLiver organoid-based Toxicity screen (LoT) is a potential assay system for liver toxicology studies, facilitating compound optimization, mechanistic study, and precision medicine as well as drug screening applications.
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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.