美国波士顿大Darrell N. Kotton等研究人员合作开发出诱导多能干细胞来源的人类肺泡2型细胞SARS-CoV-2感染模型。2020年9月18日，国际知名学术期刊《细胞—干细胞》在线发表了这一成果。

Title: SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response

Author: Jessie Huang, Adam J. Hume, Kristine M. Abo, Rhiannon B. Werder, Carlos Villacorta-Martin, Konstantinos-Dionysios Alysandratos, Mary Lou Beermann, Chantelle Simone-Roach, Jonathan Lindstrom-Vautrin, Judith Olejnik, Ellen L. Suder, Esther Bullitt, Anne Hinds, Arjun Sharma, Markus Bosmann, Ruobing Wang, Finn Hawkins, Eric J. Burks, Mohsan Saeed, Andrew A. Wilson, Elke Mühlberger, Darrell N. Kotton

Issue&Volume: 2020-09-18

Abstract: A hallmark of severe COVID-19 pneumonia is SARS-CoV-2 infection of the facultative progenitors of lung alveoli, the alveolar epithelial type 2 cells (AT2s). However, inability to access these cells from patients, particularly at early stages of disease, limits an understanding of disease inception. Here we present an in vitro human model that simulates the initial apical infection of alveolar epithelium with SARS-CoV-2, using induced pluripotent stem cell-derived AT2s that have been adapted to air-liquid interface culture. We find a rapid transcriptomic change in infected cells, characterized by a shift to an inflammatory phenotype with upregulation of NF-kB signaling and loss of the mature alveolar program. Drug testing confirms the efficacy of remdesivir as well as TMPRSS2 protease inhibition, validating a putative mechanism used for viral entry in alveolar cells. Our model system reveals cell-intrinsic responses of a key lung target cell to SARS-CoV-2 infection and should facilitate drug development.

DOI: 10.1016/j.stem.2020.09.013

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30459-8