ArticleToxicology and applied pharmacology2020
Heart slice culture system reliably demonstrates clinical drug-related cardiotoxicity.
Article in Toxicology and applied pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 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
- Advances in Living Myocardial Slice Technology for Heart Failure Research.Current heart failure reports · 2026Review
- Chemotherapy-induced cardiotoxicity in breast cancer: mechanisms, diagnostic advances, and emerging protective strategies.American journal of physiology. Heart and circulatory physiology · 2025Review
- Human induced pluripotent stem cell-derived cardiomyocytes and their use in a cardiac organ-on-a-chip to assay electrophysiology, calcium and contractility.Nature protocols · 2025Review
- Novel 2D/3D Hybrid Organoid System for High-Throughput Drug Screening in iPSC Cardiomyocytes.Therapeutics · 2025Article
- Generation and applications of cardiac spheroids.npj biomedical innovations · 2025Review
- Update on preclinical models of cancer therapy-related cardiac dysfunction: Challenges and perspectives. A scientific statement of the Heart Failure Association (HFA) of the ESC, the ESC Council of Cardio-Oncology, and the ESC Working Group on Cellular Biology of the Heart.European journal of heart failure · 2025Review
- Pharmacological or genetic inhibition of LTCC promotes cardiomyocyte proliferation through inhibition of calcineurin activity.NPJ Regenerative medicine · 2025Article
- Integral approach to organelle profiling in human iPSC-derived cardiomyocytes enhancesFrontiers in toxicology · 2025Article
- Addressing Cardiovascular Toxicity Risk of Electronic Nicotine Delivery Systems in the Twenty-First Century: "What Are the Tools Needed for the Job?" and "Do We Have Them?"Cardiovascular toxicology · 2024Review
- Editorial: Recent advances in cardiotoxicity testing, volume II.Frontiers in pharmacology · 2024Article
- A novel small molecule inhibitor of p38⍺ MAP kinase augments cardiomyocyte cell cycle entry in response to direct cell cycle stimulation.British journal of pharmacology · 2023Article
- Pharmacological or genetic inhibition of LTCC promotes cardiomyocyte proliferation through inhibition of calcineurin activity.Research square · 2023Article
- Ryanodine Receptor Staining Identifies Viable Cardiomyocytes in Human and Rabbit Cardiac Tissue Slices.International journal of molecular sciences · 2023Article
- Sarcomeric network analysis of ex vivo cultivated human atrial appendage tissue using super-resolution microscopy.Scientific reports · 2023Article
- Reproducibility of drug-induced effects on the contractility of an engineered heart tissue derived from human pluripotent stem cells.Frontiers in pharmacology · 2023Article
- Hydroxychloroquine and azithromycin alter the contractility of living porcine heart slices.Frontiers in pharmacology · 2023Article
- Living myocardial slices: Advancing arrhythmia research.Frontiers in physiology · 2023Review
- Modeling the human heart ex vivo-current possibilities and strive for future applications.Journal of tissue engineering and regenerative medicine · 2022Review
- Spectrum of National Institutes of Health-Funded Research in Cardio-Oncology: A Basic, Clinical, and Observational Science Perspective.Heart failure clinics · 2022Review
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
The limited availability of human heart tissue and its complex cell composition are major limiting factors for the reliable testing of drug efficacy and toxicity. Recently, we developed functional human and pig heart slice biomimetic culture systems that preserve the viability and functionality of 300 μm heart slices for up to 6 days. Here, we tested the reliability of this culture system for testing the cardiotoxicity of anti-cancer drugs. We tested three anti-cancer drugs (doxorubicin, trastuzumab, and sunitinib) with known different mechanisms of cardiotoxicity at three concentrations and assessed the effect of these drugs on heart slice viability, structure, function and gene expression. Slices incubated with any of these drugs for 48 h showed diminished in viability as well as loss of cardiomyocyte structure and function. Mechanistically, RNA sequencing of doxorubicin-treated tissues demonstrated a significant downregulation of cardiac genes and upregulation of oxidative stress responses. Trastuzumab treatment downregulated cardiac muscle contraction-related genes consistent with its clinically known effect on cardiomyocytes. Interestingly, sunitinib treatment resulted in significant downregulation of angiogenesis-related genes, in line with its mechanism of action. Similar to hiPS-derived-cardiomyocytes, heart slices recapitulated the expected toxicity of doxorubicin and trastuzumab, however, slices were superior in detecting sunitinib cardiotoxicity and mechanism in the clinically relevant concentration range of 0.1-1 μM. These results indicate that heart slice culture models have the potential to become a reliable platform for testing and elucidating mechanisms of drug cardiotoxicity.
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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.