Rapid Generation of Pulmonary Organoids from Induced Pluripotent Stem Cells by Co-Culturing Endodermal and Mesodermal Progenitors for Pulmonary Disease Modelling

• Published in: Biomedicines Vol. 11; no. 5; p. 1476
• Main Authors: Mitchell, Adam, Yu, Chaowen, Zhao, Xiangjun, Pearmain, Laurence, Shah, Rajesh, Hanley, Karen Piper, Felton, Timothy, Wang, Tao
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.05.2023; MDPI
• Subjects: ACE2; alveoli epithelial cells; Amino acids; Angiotensin-converting enzyme 2; anterior foregut endoderm; Aquaporin 5; Cardiomyocytes; Cell culture; Cell differentiation; Coronaviruses; COVID-19; Disease; Flow cytometry; Growth factors; Hydrogels; induced pluripotent stem cells (iPSCs); Lung diseases; mesoderm; Organoids; Phenotypes; Physiological aspects; Pluripotency; Proteins; pulmonary organoids; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Stem cells; SARS-CoV-2; iPSC disease modelling; pulmonary organoids; anterior foregut endoderm; induced pluripotent stem cells (iPSCs); mesoderm; alveoli epithelial cells
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines11051476

Differentiation of induced pluripotent stem cells to a range of target cell types is ubiquitous in monolayer culture. To further improve the phenotype of the cells produced, 3D organoid culture is becoming increasingly prevalent. Mature organoids typically require the involvement of cells from multiple germ layers. The aim of this study was to produce pulmonary organoids from defined endodermal and mesodermal progenitors. Endodermal and mesodermal progenitors were differentiated from iPSCs and then combined in 3D Matrigel hydrogels and differentiated for a further 14 days to produce pulmonary organoids. The organoids expressed a range of pulmonary cell markers such as SPA, SPB, SPC, AQP5 and T1α. Furthermore, the organoids expressed ACE2 capable of binding SARS-CoV-2 spike proteins, demonstrating the physiological relevance of the organoids produced. This study presented a rapid production of pulmonary organoids using a multi-germ-layer approach that could be used for studying respiratory-related human conditions.