用于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染建模的人诱导多能干细胞衍生肝细胞平台
Human-induced pluripotent stem cell-derived hepatocyte platform in modeling of SARS-CoV-2 infection.
作者信息
Zhang Ruiqi, Wei Rui, Yuan Yangyang, Li Na, Hu Yang, Chan Kwok-Hung, Hung Ivan Fan-Ngai, Tse Hung-Fat
机构信息
Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China.
Department of Gastroenterology and Hepatology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou China.
出版信息
JGH Open. 2024 Jul 12;8(7):e13039. doi: 10.1002/jgh3.13039. eCollection 2024 Jul.
BACKGROUND AND AIM
Currently, SARS-CoV-2 is still spreading rapidly and globally. A large proportion of patients with COVID-19 developed liver injuries. The human-induced pluripotent stem cell (iPSC)-derived hepatocytes recapitulate primary human hepatocytes and have been widely used in studies of liver diseases.
METHODS
To explore the susceptibility of hepatocytes to SARS-CoV-2, we differentiated iPSCs to functional hepatocytes and tried infecting them with different MOI (1, 0.1, 0.01) of SARS-CoV-2.
RESULTS
The iPSC-derived hepatocytes are highly susceptible to virus infection, even at 0.01 MOI. Other than the ancestral strain, iHeps also support the replication of SARS-CoV-2 variants including alpha, beta, theta, and delta. More interestingly, the ACE2 expression significantly upregulated after infection, suggesting a vicious cycle between virus infection and liver injury.
CONCLUSIONS
The iPSC-derived hepatocytes can support the replication of SARS-CoV-2, and this platform could be used to investigate the SARS-CoV-2 hepatotropism and hepatic pathogenic mechanisms.
背景与目的
目前，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）仍在全球迅速传播。很大一部分冠状病毒病（COVID-19）患者出现了肝损伤。人诱导多能干细胞（iPSC）衍生的肝细胞可重现原代人肝细胞的特性，已广泛应用于肝脏疾病研究。
方法
为探究肝细胞对SARS-CoV-2的易感性，我们将iPSC分化为功能性肝细胞，并用不同感染复数（MOI，分别为1、0.1、0.01）的SARS-CoV-2感染它们。
结果
iPSC衍生的肝细胞对病毒感染高度易感，即使在MOI为0.01时也是如此。除原始毒株外，诱导多能干细胞来源的肝细胞（iHep）也支持包括α、β、θ和δ在内的SARS-CoV-2变异株的复制。更有趣的是，感染后血管紧张素转换酶2（ACE2）表达显著上调，提示病毒感染与肝损伤之间存在恶性循环。
结论
iPSC衍生的肝细胞可支持SARS-CoV-2的复制，该平台可用于研究SARS-CoV-2的嗜肝性及肝脏致病机制。
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