Browse by author
Lookup NU author(s): Dr James Garnett
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD), a major cause of mortality and disability, is a complex disease with heterogeneous and ill-understood biological mechanisms. Human induced pluripotent stem cells (hiPSCs) are a promising tool to model human disease, including the impact of genetic susceptibility. METHODS: We developed a simple and reliable method for reprogramming peripheral blood mononuclear cells into hiPSCs and to differentiate them into air-liquid interface bronchial epithelium within 45 days. Importantly, this method does not involve any cell sorting step. We reprogrammed blood cells from one healthy control and three patients with very severe COPD. RESULTS: The mean cell purity at the definitive endoderm and ventral anterior foregut endoderm (vAFE) stages was >80%, assessed by quantifying C-X-C Motif Chemokine Receptor 4/SRY-Box Transcription Factor 17 (CXCR4/SOX17) and NK2 Homeobox 1 (NKX2.1) expression, respectively. vAFE cells from all four hiPSC lines differentiated into bronchial epithelium in air-liquid interface conditions, with large zones covered by beating ciliated, basal, goblets, club cells and neuroendocrine cells, as found in vivo. The hiPSC-derived airway epithelium (iALI) from patients with very severe COPD and from the healthy control were undistinguishable. CONCLUSIONS: iALI bronchial epithelium is ready for better understanding lung disease pathogenesis and accelerating drug discovery.
Author(s): Ahmed E, Fieldes M, Bourguignon C, Mianne J, Petit A, Jory M, Cazevieille C, Boukhaddaoui H, Garnett JP, Hirtz C, Massiera G, Vachier I, Assou S, Bourdin A, De Vos J
Publication type: Article
Publication status: Published
Journal: Cells
Year: 2022
Volume: 11
Issue: 15
Online publication date: 05/08/2022
Acceptance date: 03/08/2022
Date deposited: 15/09/2022
ISSN (electronic): 2073-4409
Publisher: MDPI
URL: https://doi.org/10.3390/cells11152422
DOI: 10.3390/cells11152422
PubMed id: 35954266
Altmetrics provided by Altmetric