Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity
Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity
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DOI：
10.1038/s41551-020-0539-4
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发表时间：
2020-04-13
影响因子：
28.1
通讯作者：
Mei, Ying
中科院分区：
文献类型：
--
作者：
Richards, Dylan J.;Li, Yang;Mei, Ying
心脏类器官包含氧扩散梯度，并用神经递质去甲肾上腺素刺激，可以模拟心肌梗死后人类心脏的结构和功能。环境因素是心血管疾病的最大贡献者。在这里，我们表明，心脏类器官，包括氧扩散梯度和刺激的神经递质去甲肾上腺素模型的心肌梗死后的人类心脏的结构（通过模仿梗死，边界和远程区域），并概括心肌梗死的标志（特别是，病理代谢变化，纤维化和钙处理）在转录组，结构和功能水平。我们还表明，类器官可以模拟缺氧增强的阿霉素心脏毒性。用非遗传病理因素模拟疾病的人类类器官可以帮助药物筛选和开发。
Cardiac organoids incorporating an oxygen-diffusion gradient and stimulated with the neurotransmitter noradrenaline can model the structure and function of the human heart after myocardial infarction.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.