Rapid Generation of Pulmonary Organoids from Induced Pluripotent Stem Cells by Co-Culturing Endodermal and Mesodermal Progenitors for Pulmonary Disease Modelling
Adam Mitchell,
Chaowen Yu,
Xiangjun Zhao,
Laurence Pearmain,
Rajesh Shah,
Karen Piper Hanley,
Timothy Felton,
Tao Wang
Affiliations
Adam Mitchell
Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK
Chaowen Yu
Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK
Xiangjun Zhao
Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK
Laurence Pearmain
Division of Diabetes, Endocrinology & Gastroenterology, Wellcome Trust Centre for Cell-Matrix Research, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK
Rajesh Shah
Manchester University Hospital NHS Foundation Trust, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LT, UK
Karen Piper Hanley
Division of Diabetes, Endocrinology & Gastroenterology, Wellcome Trust Centre for Cell-Matrix Research, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK
Timothy Felton
Division of Infection, Immunity and Respiratory Medicine, The Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK
Tao Wang
Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK
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.
