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

Shashi Kant Tiwari; Tariq M Rana

doi:10.1016/j.heliyon.2023.e19601

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

Heliyon. 2023 Aug 29;9(9):e19601. doi: 10.1016/j.heliyon.2023.e19601. eCollection 2023 Sep.

Authors

Shashi Kant Tiwari¹, Tariq M Rana¹

Affiliation

¹ Division of Genetics, Department of Pediatrics, Program in Immunology, Institute for Genomic Medicine, University of California San Diego, 9500 Gilman Drive MC 0762, La Jolla, CA, 92093, USA.

Abstract

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.

Keywords: Human iPS cells; Lung development; Lung organoids; SARS infection.