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

Dylan J. Richards, Yang Li, Charles M. Kerr, Jenny Yao, Gyda C. Beeson, Robert C. Coyle, Xun Chen, Jia Jia, Brooke Damon, Robert Wilson, E. Starr Hazard, Gary Hardiman, Donald R. Menick, Craig C. Beeson, Hai Yao, Tong Ye*, Ying Mei

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)446-462
JournalNature Biomedical Engineering
Volume4
Issue number4
DOIs
Publication statusPublished - 13 Apr 2020

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

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