Effective SARS-CoV-2 replication of monolayers of intestinal epithelial cells differentiated from human induced pluripotent stem cells

Shohei Minami; Naomi Matsumoto; Hiroko Omori; Yutaka Nakamura; Shigeyuki Tamiya; Ryotaro Nouda; Jeffery A Nurdin; Moeko Yamasaki; Tomohiro Kotaki; Yuta Kanai; Toru Okamoto; Taro Tachibana; Hiroshi Ushijima; Takeshi Kobayashi; Shintaro Sato

doi:10.1038/s41598-023-38548-1

Effective SARS-CoV-2 replication of monolayers of intestinal epithelial cells differentiated from human induced pluripotent stem cells

Sci Rep. 2023 Jul 18;13(1):11610. doi: 10.1038/s41598-023-38548-1.

Authors

Shohei Minami¹, Naomi Matsumoto¹, Hiroko Omori², Yutaka Nakamura³, Shigeyuki Tamiya³, Ryotaro Nouda¹, Jeffery A Nurdin¹, Moeko Yamasaki¹, Tomohiro Kotaki¹, Yuta Kanai¹, Toru Okamoto^{4

5}, Taro Tachibana^{6

7}, Hiroshi Ushijima⁸, Takeshi Kobayashi^{9

10}, Shintaro Sato^{11

12}

Affiliations

¹ Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan.
² Core Instrumentation Facility, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan.
³ Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, 640-8156, Japan.
⁴ Institute for Advanced Co-creation Studies, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan.
⁵ Center for Infectious Disease Education and Research, Osaka University, Osaka, 565-0871, Japan.
⁶ Cell Engineering Corporation, Osaka, 532-0011, Japan.
⁷ Department of Bioengineering, Graduate School of Engineering, Osaka Metropolitan University, Osaka, 558-8585, Japan.
⁸ Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, 173-8610, Japan.
⁹ Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan. tkobayashi@biken.osaka-u.ac.jp.
¹⁰ Center for Infectious Disease Education and Research, Osaka University, Osaka, 565-0871, Japan. tkobayashi@biken.osaka-u.ac.jp.
¹¹ Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan. shintas@wakayama-med.ac.jp.
¹² Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, 640-8156, Japan. shintas@wakayama-med.ac.jp.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe acute respiratory symptoms in humans. Controlling the coronavirus disease pandemic is a worldwide priority. The number of SARS-CoV-2 studies has dramatically increased, and the requirement for analytical tools is higher than ever. Here, we propose monolayered-intestinal epithelial cells (IECs) derived from human induced pluripotent stem cells (iPSCs) instead of three-dimensional cultured intestinal organoids as a suitable tool to study SARS-CoV-2 infection. Differentiated IEC monolayers express high levels of angiotensin-converting enzyme 2 and transmembrane protease serine 2 (TMPRSS2), host factors essential for SARS-CoV-2 infection. SARS-CoV-2 efficiently grows in IEC monolayers. Using this propagation system, we confirm that TMPRSS2 inhibition blocked SARS-CoV-2 infection in IECs. Hence, our iPSC-derived IEC monolayers are suitable for SARS-CoV-2 research under physiologically relevant conditions.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Epithelial Cells
Humans
Induced Pluripotent Stem Cells*
Intestines
SARS-CoV-2