Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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
ORCID logo ,
Rajesh Shah
,
Karen Piper Hanley
ORCID logo ,
Timothy Felton
* ,
Tao Wang
*
#
These authors contributed equally.
Version 1 : Received: 14 April 2023 / Approved: 17 April 2023 / Online: 17 April 2023 (03:33:39 CEST)

A peer-reviewed article of this Preprint also exists.

Mitchell, A.; Yu, C.; Zhao, X.; Pearmain, L.; Shah, R.; Hanley, K.P.; Felton, T.; Wang, T. Rapid Generation of Pulmonary Organoids from Induced Pluripotent Stem Cells by Co-Culturing Endodermal and Mesodermal Progenitors for Pulmonary Disease Modelling. Biomedicines 2023, 11, 1476. Mitchell, A.; Yu, C.; Zhao, X.; Pearmain, L.; Shah, R.; Hanley, K.P.; Felton, T.; Wang, T. Rapid Generation of Pulmonary Organoids from Induced Pluripotent Stem Cells by Co-Culturing Endodermal and Mesodermal Progenitors for Pulmonary Disease Modelling. Biomedicines 2023, 11, 1476.

Abstract

Differentiation of induced pluripotent stem cells to a range of useful, mature 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 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, organoids expressed ACE2 capable of binding SARS-Cov2 spike protein demonstrating the physiological relevance of the organoids produced. This study demonstrates the rapid production of pulmonary organoids using a multi-germ layer approach that could be used for studying novel respiratory disease interactions.

Keywords

pulmonary organoids; induced pluripotent stem cells (iPSCs); anterior foregut endoderm; mesoderm; alveoli epithelial cells; SARS-Cov2; iPSC disease modelling

Subject

Biology and Life Sciences, Cell and Developmental Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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