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

Nat Biomed Eng. 2020 Apr;4(4):446-462. doi: 10.1038/s41551-020-0539-4. Epub 2020 Apr 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cardiotoxicity / metabolism
  • Cardiotoxicity / pathology
  • Drug Development
  • Drug Evaluation, Preclinical / methods*
  • Heart / drug effects*
  • Humans
  • Models, Cardiovascular*
  • Myocardial Infarction / chemically induced
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / pathology*
  • Organoids / drug effects*
  • Organoids / metabolism
  • Organoids / pathology
  • Oxygen / metabolism


  • Oxygen