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人诱导多能干细胞衍生的心肌细胞平台研究 SARS-CoV-2 相关心肌损伤。

Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Platform to Study SARS-CoV-2 Related Myocardial Injury.

机构信息

Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong.

Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong.

出版信息

Circ J. 2020 Oct 23;84(11):2027-2031. doi: 10.1253/circj.CJ-20-0881. Epub 2020 Sep 26.

Abstract

BACKGROUND

SARS-CoV-2 infection is associated with myocardial injury, but there is a paucity of experimental platforms for the condition.

METHODS AND RESULTS

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) infected by SARS-CoV-2 for 3 days ceased beating and exhibited cytopathogenic changes with reduced viability. Active viral replication was evidenced by an increase in supernatant SARS-CoV-2 and the presence of SARS-CoV-2 nucleocaspid protein within hiPSC-CMs. Expressions of BNP, CXCL1, CXCL2, IL-6, IL-8 and TNF-α were upregulated, while ACE2 was downregulated.

CONCLUSIONS

Our hiPSC-CM-based in-vitro SARS-CoV-2 myocarditis model recapitulated the cytopathogenic effects and cytokine/chemokine response. It could be exploited as a drug screening platform.

摘要

背景

SARS-CoV-2 感染与心肌损伤有关,但针对这种情况的实验平台却很少。

方法和结果

感染 SARS-CoV-2 3 天的人诱导多能干细胞衍生心肌细胞(hiPSC-CMs)停止跳动,并表现出细胞病变变化,活力降低。上清液 SARS-CoV-2 增加和 hiPSC-CMs 中存在 SARS-CoV-2 核衣壳蛋白表明存在活跃的病毒复制。BNP、CXCL1、CXCL2、IL-6、IL-8 和 TNF-α 的表达上调,而 ACE2 的表达下调。

结论

我们基于 hiPSC-CM 的 SARS-CoV-2 心肌炎体外模型再现了细胞病变效应和细胞因子/趋化因子反应。它可以被开发为药物筛选平台。

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