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Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity.

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.

SUBMITTER: Richards DJ

PROVIDER: S-EPMC7422941 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity.

Richards Dylan J DJ Li Yang Y Kerr Charles M CM Yao Jenny J Beeson Gyda C GC Coyle Robert C RC Chen Xun X Jia Jia J Damon Brooke B Wilson Robert R Starr Hazard E E Hardiman Gary G Menick Donald R DR Beeson Craig C CC Yao Hai H Ye Tong T Mei Ying Y

Nature biomedical engineering 20200413 4

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, s ...[more]

PMID: 32284552

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