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

doi:10.1038/s41551-020-0539-4

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

Queen's University Belfast

Research output: Contribution to journal › Article › peer-review

286 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 language	English
Pages (from-to)	446-462
Journal	Nature Biomedical Engineering
Volume	4
Issue number	4
DOIs	https://doi.org/10.1038/s41551-020-0539-4
Publication status	Published - 13 Apr 2020

ASJC Scopus subject areas

Biotechnology
Bioengineering
Medicine (miscellaneous)
Biomedical Engineering
Computer Science Applications

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41551-020-0539-4

Gary Hardiman
- G.Hardimanqub.acuk
- School of Biological Sciences - Professor
- Institute for Global Food Security
Person: Academic

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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. (2020). Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity. Nature Biomedical Engineering, 4(4), 446-462. https://doi.org/10.1038/s41551-020-0539-4

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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.",

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

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doi = "10.1038/s41551-020-0539-4",

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Richards, DJ, Li, Y, Kerr, CM, Yao, J, Beeson, GC, Coyle, RC, Chen, X, Jia, J, Damon, B, Wilson, R, Starr Hazard, E, Hardiman, G, Menick, DR, Beeson, CC, Yao, H, Ye, T & Mei, Y 2020, 'Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity', Nature Biomedical Engineering, vol. 4, no. 4, pp. 446-462. https://doi.org/10.1038/s41551-020-0539-4

TY - JOUR

T1 - Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity

AU - Richards, Dylan J.

AU - Li, Yang

AU - Kerr, Charles M.

AU - Yao, Jenny

AU - Beeson, Gyda C.

AU - Coyle, Robert C.

AU - Chen, Xun

AU - Jia, Jia

AU - Damon, Brooke

AU - Wilson, Robert

AU - Starr Hazard, E.

AU - Hardiman, Gary

AU - Menick, Donald R.

AU - Beeson, Craig C.

AU - Yao, Hai

AU - Ye, Tong

AU - Mei, Ying

PY - 2020/4/13

Y1 - 2020/4/13

N2 - 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.

AB - 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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DO - 10.1038/s41551-020-0539-4

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EP - 462

JO - Nature Biomedical Engineering

JF - Nature Biomedical Engineering

IS - 4

ER -

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

Abstract

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Gary Hardiman

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