Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity
Top Cited Papers
- 12 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Biomedical Engineering
- Vol. 4 (4), 446-462
- https://doi.org/10.1038/s41551-020-0539-4
Abstract
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.Keywords
Funding Information
- U.S. Department of Health & Human Services | National Institutes of Health
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