Human airway lineages derived from pluripotent stem cells reveal the epithelial responses to SARS-CoV-2 infection.

Autor:	Wang R; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts.; Division of Pulmonary Medicine, Boston Children's Hospital, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts., Hume AJ; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts.; National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts., Beermann ML; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts.; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts., Simone-Roach C; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts.; Division of Pulmonary Medicine, Boston Children's Hospital, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts., Lindstrom-Vautrin J; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts., Le Suer J; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts.; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts., Huang J; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts.; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts., Olejnik J; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts.; National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts., Villacorta-Martin C; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts., Bullitt E; Department of Physiology & Biophysics, Boston University, Boston, Massachusetts., Hinds A; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts., Ghaedi M; Research and Early Development Respiratory & Inflammation (R&I), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland., Rollins S; Division of Pulmonary Medicine, Boston Children's Hospital, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts., Werder RB; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts.; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.; QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia., Abo KM; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts.; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts., Wilson AA; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts.; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts., Mühlberger E; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts.; National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts., Kotton DN; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts.; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.; Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts., Hawkins FJ; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts.; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2022 Mar 01; Vol. 322 (3), pp. L462-L478. Date of Electronic Publication: 2022 Jan 12.
DOI:	10.1152/ajplung.00397.2021
Abstrakt:	There is an urgent need to understand how SARS-CoV-2 infects the airway epithelium and in a subset of individuals leads to severe illness or death. Induced pluripotent stem cells (iPSCs) provide a near limitless supply of human cells that can be differentiated into cell types of interest, including airway epithelium, for disease modeling. We present a human iPSC-derived airway epithelial platform, composed of the major airway epithelial cell types, that is permissive to SARS-CoV-2 infection. Subsets of iPSC-airway cells express the SARS-CoV-2 entry factors angiotensin-converting enzyme 2 ( ACE2 ), and transmembrane protease serine 2 ( TMPRSS2 ). Multiciliated cells are the primary initial target of SARS-CoV-2 infection. On infection with SARS-CoV-2, iPSC-airway cells generate robust interferon and inflammatory responses, and treatment with remdesivir or camostat mesylate causes a decrease in viral propagation and entry, respectively. In conclusion, iPSC-derived airway cells provide a physiologically relevant in vitro model system to interrogate the pathogenesis of, and develop treatment strategies for, COVID-19 pneumonia.
Databáze:	MEDLINE
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