Human Induced Pluripotent Stem Cell-Derived Lung Epithelial System for SARS-CoV-2 Infection Modeling and Its Potential in Drug Repurposing

人类诱导性多能干细胞来源的肺上皮系统用于 SARS-CoV-2 感染建模及其在药物再利用中的潜力

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作者:Harshini Surendran, Swapna Nandakumar, Rajarshi Pal

Abstract

The lung is the most vulnerable target for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and respiratory failure causing acute respiratory distress syndrome is its foremost outcome. However, the current primary in vitro models in use for SARS-CoV-2 display apparent limitations for modeling such complex human respiratory disease. Although patient cells can directly model the effects of a drug, their availability and capacity for expansion are limited compared with transformed/immortalized cells or tumor-derived cell lines. An additional caveat is that the latter may harbor genetic and metabolic abnormalities making them unsuitable for drug screening. Therefore, it is important to create physiologically relevant human-cell models that can replicate the pathophysiology of SARS-CoV-2, thus facilitating drug testing. In this study, we show preliminary data on how human induced pluripotent stem cells-derived lung epithelial cell system could emerge as a relevant and sensitive platform for modeling SARS-CoV-2 infection and drug screening.

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