Generation of 3D lung organoids from human induced pluripotent stem cells for modeling of lung development and viral infection

The lack of physiologically relevant in vitro models has hampered progress in understanding human lung development and disease. Here, we describe a protocol in which human induced pluripotent stem cells (hiPSCs) undergo stepwise differentiation into definitive endoderm (>88% population) to three-...

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Detalles Bibliográficos
Autores principales: Tiwari, Shashi Kant, Rana, Tariq M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10558843/
https://www.ncbi.nlm.nih.gov/pubmed/37809493
http://dx.doi.org/10.1016/j.heliyon.2023.e19601
Descripción
Sumario:The lack of physiologically relevant in vitro models has hampered progress in understanding human lung development and disease. Here, we describe a protocol in which human induced pluripotent stem cells (hiPSCs) undergo stepwise differentiation into definitive endoderm (>88% population) to three-dimensional (3D) lung organoids (LORGs), which contain both epithelial and mesenchymal cellular architecture and display proximal and distal airway patterning. These LORGs can maintained for more than 90 days by re-embedding in the Matrigel. We show the utility of LORGs for disease modeling and drug screening by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and treatment with antiviral drugs.

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