Establishment of human distal lung organoids for SARS-CoV-2 infection
Ting Wang, Ning Zhang, Shipan Fan, Lianzheng Zhao, Wanlu Song, Yuhuan Gong, Quan Shen, Cheng Zhang, Peng Ren, Chutong Lin, Wei Fu, George F. Gao, Shaohua Ma, Yuhai Bi, Ye‐Guang Chen
Abstract
Dear Editor, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is being a serious pandemic with more than 164 million infections and 3.41 million deaths in over 200 countries as of 20 May 2021. This deadly disease mainly affects the respiratory system, gastrointestinal tract, and nervous system. To understand the mechanisms underlying SARS-CoV-2 infection and develop effective medicines, appropriate models that can be used to faithfully mimic viral infection in the human body are urgently needed. Several cell lines have been commonly used to investigate infection susceptibilities, virus infection, replication mechanism and to screen antiviral drugs 1,2 . Mouse models expressing human ACE2 and hamsters have also been used to imitate the SARS-CoV-2 infection 3 . However, both cell lines and animal models have limitations and cannot accurately capture the key characteristics of human biology. As a new type of research model, human pluripotent stem cells (hPSCs)-derived organoids, like lung, colon, brain have been used for SARS-CoV-2 infection 4,5 . However, these hPSC-derived organoids represent a fetal phenotype but not a fully mature state in adults. Human lung alveolar type 2 cells-based 3D cultures, human 2D air-liquid interface bronchioalveolar and human small intestinal organoid models were also used Here, we established human distal lung organoids (hDLO) from