한빛사논문
- 조회1,553
Han Kyung Kima,b,c,1, Hyeryeon Kimd,1, Myoung Kyu Leee,1, Woo Hee Choia,b, Yejin Jange, Jin Soo Shine, Jun-Yeol Parka,b, Dong Hyuck Baea,b, Seong-In Hyuna, Kang Hyun Kimf, Hyun Wook Hanf, Byungho Limg, Gildon Choig,h, Meehyein Kime,i,***, Young Chang Limd,**, Jongman Yooa,b,c,*
aDepartment of Microbiology, CHA University School of Medicine, Seongnam, Republic of Korea bCHA Organoid Research Center, CHA University, Seongnam, Republic of Korea cR&D Institute, Organoidsciences Ltd., Seongnam, Republic of Korea dDepartment of Otorhinolaryngology-Head and Neck Surgery, The Research Institute, Konkuk University School of Medicine, Seoul, Republic of Korea eInfectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea fDepartment of Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam, Republic of Korea gData Convergence Drug Research Center, KRICT, Daejeon, Republic of Korea hDepartment of Medicinal Chemistry and Pharmacology, University of Science and Technology (UST), Daejeon, Republic of Korea iGraduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Republic of Korea
*Corresponding author. Department of Microbiology, CHA University School of Medicine, Seongnam, Republic of Korea.
**Corresponding author. Department of Otorhinolaryngology-Head and Neck Surgery, the Research Institute, Konkuk University School of Medicine, Seoul, Republic of Korea.
***Corresponding author. Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea.
1These authors contributed equally to this work.
Abstract
The palatine tonsils (hereinafter referred to as “tonsils”) serve as a reservoir for viral infections and play roles in the immune system's first line of defense. The aims of this study were to establish tonsil epithelial cell–derived organoids and examine their feasibility as an ex vivo model for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The tonsil organoids successfully recapitulated the key characteristics of the tonsil epithelium, including cellular composition, histologic properties, and biomarker distribution. Notably, the basal layer cells of the organoids express molecules essential for SARS-CoV-2 entry, such as angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) and furin, being susceptible to the viral infection. Changes in the gene expression profile in tonsil organoids revealed that 395 genes associated with oncostatin M signaling and lipid metabolism were highly upregulated within 72 h after SARS-CoV-2 infection. Notably, remdesivir suppressed the viral RNA copy number in organoid culture supernatants and intracellular viral protein levels in a dose-dependent manner. Here, we suggest that tonsil epithelial organoids could provide a preclinical and translational research platform for investigating SARS-CoV-2 infectivity and transmissibility or for evaluating antiviral candidates.
논문정보
- Research article
- 2022년 04월 (BRIC 등록일 2022-03-22)
- 국내 연구진
- 의약학 > 재생의학
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