SARS-CoV-2 infects an upper airway model derived from induced pluripotent stem cells.
SARS-CoV-2 infects an upper airway model derived from induced pluripotent stem cells.
复制标题
DOI：
10.1002/stem.3422
复制
发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Armstrong L
中科院分区：
文献类型：
--
作者：
Djidrovski I;Georgiou M;Hughes GL;Patterson EI;Casas-Sanchez A;Pennington SH;Biagini GA;Moya-Molina M;van den Bor J;Smit MJ;Chung G;Lako M;Armstrong L
作为异生物质物质和感染剂进入体内的主要入口之一，肺受到一系列功能障碍和疾病的影响，这些疾病共同导致大量患者死亡。鉴于此，存在对体外系统的突出需求，在体外系统中评估肺的感染因子和异生物质物质的影响。为了解决这个问题，我们已经开发了一种方案，从诱导多能干细胞产生气道上皮基底样细胞，这简化了人类上呼吸道细胞模型的制造。本研究中产生的基底样细胞在transwell插入物上培养，以形成融合的单层细胞，然后暴露于气液界面，诱导分化为假复层上皮结构，其与体内上气道上皮具有显著的相似性。这些构建体包含上皮模型系统所需的组成细胞类型，产生粘液和功能性纤毛，并且可以以类似于体内气道的方式支持SARS-CoV-2感染/复制和细胞因子的分泌。这种方法提供了一种易于获得和高度可扩展的方案，用于制造上呼吸道模型，该模型可以应用于呼吸道病毒感染的治疗方法的开发和对人类肺部药物毒性的评估。我们已经开发了一种从诱导多能干细胞产生气道上皮基底样细胞的方案，其简化了人类上呼吸道的细胞模型的制造，所述细胞模型能够支持SARS-CoV-2感染/复制和以类似于体内气道的方式分泌细胞因子。
As one of the primary points of entry of xenobiotic substances and infectious agents into the body, the lungs are subject to a range of dysfunctions and diseases that together account for a significant number of patient deaths. In view of this, there is an outstanding need for in vitro systems in which to assess the impact of both infectious agents and xenobiotic substances of the lungs. To address this issue, we have developed a protocol to generate airway epithelial basal-like cells from induced pluripotent stem cells, which simplifies the manufacture of cellular models of the human upper airways. Basal-like cells generated in this study were cultured on transwell inserts to allow formation of a confluent monolayer and then exposed to an air-liquid interface to induce differentiation into a pseudostratified epithelial construct with a marked similarity to the upper airway epithelium in vivo. These constructs contain the component cell types required of an epithelial model system, produce mucus and functional cilia, and can support SARS-CoV-2 infection/replication and the secretion of cytokines in a manner similar to that of in vivo airways. This method offers a readily accessible and highly scalable protocol for the manufacture of upper airway models that could find applications in development of therapies for respiratory viral infections and the assessment of drug toxicity on the human lungs. We have developed a protocol to generate airway epithelial basal-like cells from induced pluripotent stem cells, which simplifies the manufacture of cellular models of the human upper airways that are capable of supporting SARS-CoV-2 infection/replication and the secretion of cytokines in a manner similar to that of in vivo airways.
登录
查看更多内容
影响因子：
5.4
作者：
Glowacka, Ilona;Bertram, Stephanie;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
影响因子：
64.8
作者：
Montoro DT;Haber AL;Biton M;Vinarsky V;Lin B;Birket SE;Yuan F;Chen S;Leung HM;Villoria J;Rogel N;Burgin G;Tsankov AM;Waghray A;Slyper M;Waldman J;Nguyen L;Dionne D;Rozenblatt-Rosen O;Tata PR;Mou H;Shivaraju M;Bihler H;Mense M;Tearney GJ;Rowe SM;Engelhardt JF;Regev A;Rajagopal J
通讯作者：
Rajagopal J
影响因子：
64.8
作者：
Imai Y;Kuba K;Rao S;Huan Y;Guo F;Guan B;Yang P;Sarao R;Wada T;Leong-Poi H;Crackower MA;Fukamizu A;Hui CC;Hein L;Uhlig S;Slutsky AS;Jiang C;Penninger JM
通讯作者：
Penninger JM
影响因子：
82.9
作者：
Kuba K;Imai Y;Rao S;Gao H;Guo F;Guan B;Huan Y;Yang P;Zhang Y;Deng W;Bao L;Zhang B;Liu G;Wang Z;Chappell M;Liu Y;Zheng D;Leibbrandt A;Wada T;Slutsky AS;Liu D;Qin C;Jiang C;Penninger JM
通讯作者：
Penninger JM
DOI：
10.1038/nrmicro2090
发表时间：
2009-03
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--