人心肌类器官用于心肌梗死和药物心脏毒性的建模。
Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity.
机构信息
Bioengineering Department, Clemson University, Clemson, SC, USA.
Immunology Translational Sciences, Janssen Research and Development, LLC, Spring House, PA, USA.
出版信息
Nat Biomed Eng. 2020 Apr;4(4):446-462. doi: 10.1038/s41551-020-0539-4. Epub 2020 Apr 13.
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.
摘要
环境因素是心血管疾病的最大诱因。在这里，我们展示了一种包含氧扩散梯度的心脏类器官，它受到神经递质去甲肾上腺素的刺激，模拟了心肌梗死后人类心脏的结构（通过模拟梗死、边缘和远程区域），并在转录组、结构和功能水平上再现了心肌梗死的特征（特别是病理性代谢转变、纤维化和钙处理）。我们还表明，类器官可以模拟缺氧增强的阿霉素心脏毒性。能够模拟具有非遗传病理因素的疾病的人类类器官可能有助于药物筛选和开发。
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