ArticleScientific reports2017
Patient-specific hepatocyte-like cells derived from induced pluripotent stem cells model pazopanib-mediated hepatotoxicity.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- A comprehensive transcriptomic comparison of hepatocyte model systems improves selection of models for experimental use.Communications biology · 2022Pooled it
- A Phase I/II Study to Assess the Safety and Efficacy of Pazopanib and Pembrolizumab Combination Therapy in Patients with Advanced Renal Cell Carcinoma.Clinical genitourinary cancer · 2021Trial
- Improving hepatic metabolic function with 3D iPSC-derived human hepatocytes.Cell biology and toxicology · 2026Article
- The evolving landscape of pharmacogenomics: Current achievements and future directions.Pharmacological reviews · 2026Review
- Investigating the Mechanisms of Pazopanib-induced Hepatotoxicity: Insights from Network Toxicology, Microarray Analysis, and Machine Learning.Current medicinal chemistry · 2026Article
- Nutrient environment improves drug metabolic activity in human iPSC-derived hepatocytes and HepG2.Archives of toxicology · 2025Article
- Review
- Impact of nephrotoxins and oxidants on survival and transport function of hiPSC-derived renal proximal tubular cells.Archives of toxicology · 2025Article
- Comparative transcriptomic and phenotypic analysis of induced pluripotent stem cell hepatocyte-like cells and primary human hepatocytes.Cell and tissue research · 2024Article
- Review on kidney diseases: types, treatment and potential of stem cell therapy.Renal replacement therapy · 2023Review
- In Vitro Models for Studying Chronic Drug-Induced Liver Injury.International journal of molecular sciences · 2022Review
- Using liver models generated from human-induced pluripotent stem cells (iPSCs) for evaluating chemical-induced modifications and disease across liver developmental stages.Toxicology in vitro : an international journal published in association with BIBRA · 2022Review
- Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction.Acta pharmaceutica Sinica. B · 2021Review
- Human Pluripotent Stem Cell-Derived Hepatocyte-Like Cells and Organoids for Liver Disease and Therapy.International journal of molecular sciences · 2021Review
- Protective effects of taxifolin on pazopanib-induced liver toxicity: an experimental rat model.Experimental animals · 2021Article
- Human biomimetic liver microphysiology systems in drug development and precision medicine.Nature reviews. Gastroenterology & hepatology · 2021Review
- A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice.Xenobiotica; the fate of foreign compounds in biological systems · 2019Article
- Human-relevant preclinical in vitro models for studying hepatobiliary development and liver diseases using induced pluripotent stem cells.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Progress, obstacles, and limitations in the use of stem cells in organ-on-a-chip models.Advanced drug delivery reviews · 2019Review
- Toxicogenomics: A 2020 Vision.Trends in pharmacological sciences · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Idiosyncratic drug-induced hepatotoxicity is a major cause of liver damage and drug pipeline failure, and is difficult to study as patient-specific features are not readily incorporated in traditional hepatotoxicity testing approaches using population pooled cell sources. Here we demonstrate the use of patient-specific hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells for modeling idiosyncratic hepatotoxicity to pazopanib (PZ), a tyrosine kinase inhibitor drug associated with significant hepatotoxicity of unknown mechanistic basis. In vitro cytotoxicity assays confirmed that HLCs from patients with clinically identified hepatotoxicity were more sensitive to PZ-induced toxicity than other individuals, while a prototype hepatotoxin acetaminophen was similarly toxic to all HLCs studied. Transcriptional analyses showed that PZ induces oxidative stress (OS) in HLCs in general, but in HLCs from susceptible individuals, PZ causes relative disruption of iron metabolism and higher burden of OS. Our study establishes the first patient-specific HLC-based platform for idiosyncratic hepatotoxicity testing, incorporating multiple potential causative factors and permitting the correlation of transcriptomic and cellular responses to clinical phenotypes. Establishment of patient-specific HLCs with clinical phenotypes representing population variations will be valuable for pharmaceutical drug testing.
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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.