Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity
Open accessAbstract
Environmental factors are the largest contributors to cardiovascular disease. Here we show that cardiac organoids that incorporate an oxygen-diffusion gradient and that are stimulated with the neurotransmitter noradrenaline model the structure of the human heart after myocardial infarction (by mimicking the infarcted, border and remote zones), and recapitulate hallmarks of myocardial infarction (in particular, pathological metabolic shifts, fibrosis and calcium handling) at the transcriptomic, structural and functional levels. We also show that the organoids can model hypoxia-enhanced doxorubicin cardiotoxicity. Human organoids that model diseases with non-genetic pathological factors could help with drug screening and development.
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Multi-cell-type in vitro models such as spheroids, organoids, and engineered heart tissue are proficient in generating force and exhibit predictable responses to pharmacological agents.
“These models are proficient in generating force and exhibit predictable responses to pharmacological agents.[ 23 , 24 ]”
From Engineered in vitro multi-cell type ventricle model generates long-term pulsatile flow and modulates cardiac output in response to cardioactive drugs (2025) · cites this paper as [24]
The Results sections on heart-failure drug testing and drug-induced cardiotoxicity report beating cardiac organoids and responses to JQ1 and doxorubicin. But the paper measures contraction amplitude rather than generated force, and its Methods define spheroids as monocellular; it does not establish the claim for all three model types, including engineered heart tissue. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSpheroid cultures have enabled the engineering of heart, liver, and lung fibrosis models.
“For example, spheroid cultures have enabled the engineering of heart, liver, and lung fibrosis models6,15–18”
From 3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels (2021) · cites this paper as [6]
Engineered cardiac tissues are being widely used as models to study drug toxicities and efficacy in vitro.
“Engineered cardiac tissues are being widely used as models to study drug toxicities and efficacy in vitro6,43–45,60.”
From 3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels (2021) · cites this paper as [6]
Tissue engineering approaches for heart-on-a-chip or heart organoid models allow high control of the end construct but tend to be expensive, work-intensive, and not readily scalable.
“While these approaches allow for high control of the end construct, they tend to be expensive, work-intensive, and not readily scalable.”
From Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease (2021) · cites this paper as [9]
Tissue engineering approaches frequently do not faithfully represent the original cell composition and organization of the heart.
“Furthermore, they frequently do not faithfully represent the original cell composition (e.g., use of dermal fibroblasts or HUVECs)8,9 and organization (e.g., cardiospheres10,11) of the heart.”
From Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease (2021) · cites this paper as [9]
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Cardioids reveal self-organizing principles of human cardiogenesis
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- Authors
- Richards, D. J., Li, Y., Kerr, C. M., Yao, J., Beeson, G. C., Coyle, R. C., Chen, X., Jia, J., Damon, B., Wilson, R., Starr Hazard, E., Hardiman, G., Menick, D. R., Beeson, C. C., Yao, H., Ye, T., & Mei, Y.
- Affiliations
- Janssen Research & Development (United States) (US)
- Clemson University (US)
- Medical University of South Carolina (US)
- Harvard University (US)
- Queen's University Belfast (GB)
- Corresponding author
- Ye, Tong
- Mei, Ying
- ORCID
- Venue
- Nature Biomedical Engineering
- Published
- 2020-04-13
- Volume
- 4
- Issue
- 4
- Pages
- 446-462
- ISSN
- 2157-846X (ISSN-L)
- PMC
- PMC7422941
- OpenAlex
- W3015284544
- Cited by
- 439
- References
- 106
- Citations by year
- 2026: 56 · 2025: 84 · 2024: 68 · 2023: 73 · 2022: 80 · 2021: 63 · 2020: 14
- FWCI
- 52.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Biomedical Engineering (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- cardiac organoids, myocardial infarction, drug-induced cardiotoxicity, doxorubicin cardiotoxicity, hypoxia, myocardial fibrosis, calcium handling, metabolic reprogramming, drug screening
- MeSH terms
- Drug Development, Drug Evaluation, Preclinical, Heart, Humans, Models, Cardiovascular, Myocardial Infarction, Organoids, Oxygen, Cardiotoxicity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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