Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 149, Issue 3, Pages -Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2022.04.010
Keywords
COVID-19; SARS-CoV-2; iPSC; Small intestinal epithelial cells; Barrier functions
Categories
Funding
- Ministry of Education, Culture, Sports, Science, and Technology, Japan [21H02634]
- Research on Regulatory Harmonization and Evaluation of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics from Japan Agency for Medical Research and Development, AMED [JP21mk0101189]
- Emerging and Re-emerging Infectious Diseases, AMED [JP20fk0108518]
- Smoking Research Foundation
- Grants-in-Aid for Scientific Research [21H02634] Funding Source: KAKEN
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This study investigated the use of human induced pluripotent stem cell-derived small intestinal epithelial cells (iPSC-SIECs) as a model for SARS-CoV-2 infection. The results showed that iPSC-SIECs can be infected by SARS-CoV-2 and that treatment with remdesivir reduces viral replication. The study also found that SARS-CoV-2 infection affects tight junction markers and increases the expression of proinflammatory genes.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), has rapidly spread and led to global health crises. COVID-19 causes well-known respiratory failure and gastrointestinal symptoms, such as diarrhea, nausea, and vomiting. Thus, human gastrointestinal cell models are urgently needed for COVID-19 research; however, it is difficult to obtain primary human intestinal cells. In this study, we examined whether human induced pluripotent stem cell (iPSC)derived small intestinal epithelial cells (iPSC-SIECs) could be used as a SARS-CoV-2 infection model. We observed that iPSC-SIECs, such as absorptive and Paneth cells, were infected with SARS-CoV-2, and remdesivir treatment decreased intracellular SARS-CoV-2 replication in iPSC-SIECs. SARS-CoV-2 infection decreased expression levels of tight junction markers, ZO-3 and CLDN1, and transepithelial electrical resistance (TEER), which evaluates the integrity of tight junction dynamics. In addition, SARS-CoV-2 infection increased expression levels of proinflammatory genes, which are elevated in patients with COVID-19. These findings suggest iPSC-SIECs as a useful in vitro model for elucidating COVID-19 pathology and drug development. (c) 2022 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
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