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体外肺泡模型揭示SARS-CoV-2致病机理
2020-10-25 21:57

美国杜克大学医学院的Purushothama Rao Tata课题组利用基于人类肺干细胞的肺泡球揭示了SARS-CoV-2介导的干扰素应答和肺细胞功能障碍。2020年10月21日,国际知名学术期刊《细胞—干细胞》在线发表了这一成果。

研究人员报告了无滋养层、可扩增、化学定义和模块化的肺泡培养系统,可用于培养和分化来源于原发性肺组织的人类肺泡2型细胞/肺细胞。培养的肺细胞表达SARS-CoV-2受体ACE2,因此可以感染病毒。感染肺泡球的转录组和组织学分析反映了COVID-19肺的特征,包括干扰素介导的炎症反应的出现、表面活性剂蛋白的丢失和细胞凋亡。用干扰素治疗肺泡球概括了病毒感染的特征,包括细胞死亡。
 
相反,用低剂量IFN预处理的肺泡球显示病毒复制减少,这表明IFN可以预防SARS-CoV-2。因此,基于人类干细胞的肺泡球提供了有关COVID-19发病机理的新见解,并可作为理解人类呼吸系统疾病的模型。
 
据悉,冠状病毒感染引起弥漫性肺泡损伤,从而导致急性呼吸窘迫综合征。人肺泡上皮体外模型的缺乏阻碍了对COVID-19发病机制的理解。
 
附:英文原文

Title: Human lung stem cell-based alveolospheres provide insights into SARS-CoV-2 mediated interferon responses and pneumocyte dysfunction

Author: Hiroaki Katsura, Vishwaraj Sontake, Aleksandra Tata, Yoshihiko Kobayashi, Caitlin E. Edwards, Brook E. Heaton, Arvind Konkimalla, Takanori Asakura, Yu Mikami, Ethan J. Fritch, Patty J. Lee, Nicholas S. Heaton, Richard C. Boucher, Scott H. Randell, Ralph S. Baric, Purushothama Rao Tata

Issue&Volume: 2020-10-21

Abstract: Coronavirus infection causes diffuse alveolar damage leading to acute respiratory distress syndrome. The absence of ex vivo models of human alveolar epithelium is hindering an understanding of COVID-19 pathogenesis. We report a feeder-free, scalable, chemically-defined, and modular alveolosphere culture system for propagation and differentiation of human alveolar type 2 cells/pneumocytes derived from primary lung tissue. Cultured pneumocytes express the SARS-CoV-2 receptor ACE2 and can be infected with virus. Transcriptome and histological analysis of infected alveolospheres mirrors features of COVID-19 lungs, including emergence of interferon mediated inflammatory responses, loss of surfactant proteins, and apoptosis. Treatment of alveolospheres with interferons recapitulates features of virus infection, including cell death. In contrast, alveolospheres pretreated with low dose IFNs show a reduction in viral replication, suggesting the prophylactic effectiveness of IFNs against SARS-CoV-2. Human stem cell-based alveolospheres thus provide novel insights into COVID-19 pathogenesis and can serve as a model for understanding human respiratory diseases.

DOI: 10.1016/j.stem.2020.10.005

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30499-9

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:25.269
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx


本期文章:《细胞—干细胞》:Online/在线发表

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