ArticleBiomaterials2018
Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system.
Article in Biomaterials, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.
- Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes as an in vitro model in toxicology: strengths and weaknesses for hazard identification and risk characterization.Expert opinion on drug metabolism & toxicology · 2021Pooled it
- Targeting histamine signaling: repurposing antihistamines for cancer chemotherapy and immunotherapy.Archives of pharmacal research · 2026Review
- Clinical trials in a dish: cardiometabolic drug development with biological and digital twins.The Journal of clinical investigation · 2026Review
- Reverse bioengineering of the liver: developmental principles for next-generation liver-on-a-chip systems.Communications biology · 2026Review
- Advanced in vitro cardiac models for drug evaluation: integration of organoids, engineered tissues, and microphysiological systems.Microsystems & nanoengineering · 2026Review
- A Tri-Culture Heart-on-a-Chip Platform With iPSC-Derived Cardiac Cells for Predictive Cardiotoxicity Testing.Advanced healthcare materials · 2026Article
- Organ-on-a-Chip Technology and Global Multi-Omics: Current Applications and Future Directions.MedComm · 2026Review
- The 3D landscape of infection: spatial organization andFrontiers in immunology · 2026Review
- Human Multi-Organ-on-a-Chip Platforms for Next-Generation Drug Delivery Strategies.Theranostics · 2026Review
- Organ-on-a-Chip and Lab-on-a-Chip Technologies in Cardiac Tissue Engineering.Biomimetics (Basel, Switzerland) · 2025Review
- Integrating Bioprinting and Increased Throughput: Next-Generation Models for Cardiac Research.International journal of molecular sciences · 2025Review
- Numerical models for organ-on-a-chip: A systematic review and analyses.Biomicrofluidics · 2025Review
- Pharmacists' Perceptions of 3D Printing and Bioprinting as Part of Personalized Pharmacy: A Cross-Sectional Pilot Study in Bulgaria.Pharmacy (Basel, Switzerland) · 2025Article
- An eighteen-organ microphysiological system coupling a vascular network and excretion system for drug discovery.Microsystems & nanoengineering · 2025Article
- Advances in humanoid organoid-based research on inter-organ communications during cardiac organogenesis and cardiovascular diseases.Journal of translational medicine · 2025Review
- Current hPSC-derived liver organoids for toxicity testing: Cytochrome P450 enzymes and drug metabolism.Toxicological research · 2025Review
- Fetal bovine serum: how to leave it behind in the pursuit of more reliable science.Frontiers in toxicology · 2025Review
- Tissue chips as headway model and incitement technology.Synthetic and systems biotechnology · 2025Review
- Targeted Cancer Therapy-on-A-Chip.Advanced healthcare materials · 2024Review
- Cell cycle visualization tools to study cardiomyocyte proliferation in real-time.Open biology · 2024Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
Abstract
Regulation of cosmetic testing and poor predictivity of preclinical drug studies has spurred efforts to develop new methods for systemic toxicity. Current in vitro assays do not fully represent physiology, often lacking xenobiotic metabolism. Functional human multi-organ systems containing iPSC derived cardiomyocytes and primary hepatocytes were maintained under flow using a low-volume pumpless system in a serum-free medium. The functional readouts for contractile force and electrical conductivity enabled the non-invasive study of cardiac function. The presence of the hepatocytes in the system induced cardiotoxic effects from cyclophosphamide and reduced them for terfenadine due to drug metabolism, as expected from each compound's pharmacology. A computational fluid dynamics simulation enabled the prediction of terfenadine-fexofenadine pharmacokinetics, which was validated by HPLC-MS. This in vitro platform recapitulates primary aspects of the in vivo crosstalk between heart and liver and enables pharmacological studies, involving both organs in a single in vitro platform. The system enables non-invasive readouts of cardiotoxicity of drugs and their metabolites. Hepatotoxicity can also be evaluated by biomarker analysis and change in metabolic function. Integration of metabolic function in toxicology models can improve adverse effects prediction in preclinical studies and this system could also be used for chronic studies as well.
Indexed as
Identifiers
What OpenQuestion holds
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.