ヒトiPS細胞由来の肺胞上皮細胞を用いたSARS-CoV-2感染

抄録

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 entry to host cells are initiated by binding with its receptor, angiotensin-converting enzyme 2 (ACE2), and the ACE2 abundance is thought to reflect the susceptibility to infection. ACE2 is expressed in various types of cells, such as lung, heart, liver, cornea and ileum. Especially, respiratory cells are considered important in terms of clinical outcome. Thus, supplying human respiratory cells, such as airway basal, club, ciliated and alveolar epithelial type II (ATII) cells, is essential for COVID-19 research. However, differentiation methods of human ACE2-expressing respiratory cells has not been fully understood. In the present study, we have generated ATII cells from human iPSCs using two-dimensional culture method. We differentiated human iPSCs using a stepwise protocol. After making lung progenitor cells from human iPSCs, alveolar cells were induced by further culture in the presence of chemicals. RT-qPCR and immunofluorescence analysis revealed that the differentiated cells contained SFTPB-positive ATII cells and expressed ACE2. In addition, the cells were infected with SARS-CoV-2. These data suggest that the iPSC-derived alveolar cell is a good in vitro model for COVID-19 research.