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Differentiation of Human Induced Pluripotent Stem Cells from Patients with Severe COPD into Functional Airway Epithelium

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 ge...

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Autores principales: Ahmed, Engi, Fieldes, Mathieu, Bourguignon, Chloé, Mianné, Joffrey, Petit, Aurélie, Jory, Myriam, Cazevieille, Chantal, Boukhaddaoui, Hassan, Garnett, James P., Hirtz, Christophe, Massiera, Gladys, Vachier, Isabelle, Assou, Said, Bourdin, Arnaud, De Vos, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368529/
https://www.ncbi.nlm.nih.gov/pubmed/35954266
http://dx.doi.org/10.3390/cells11152422
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author Ahmed, Engi
Fieldes, Mathieu
Bourguignon, Chloé
Mianné, Joffrey
Petit, Aurélie
Jory, Myriam
Cazevieille, Chantal
Boukhaddaoui, Hassan
Garnett, James P.
Hirtz, Christophe
Massiera, Gladys
Vachier, Isabelle
Assou, Said
Bourdin, Arnaud
De Vos, John
author_facet Ahmed, Engi
Fieldes, Mathieu
Bourguignon, Chloé
Mianné, Joffrey
Petit, Aurélie
Jory, Myriam
Cazevieille, Chantal
Boukhaddaoui, Hassan
Garnett, James P.
Hirtz, Christophe
Massiera, Gladys
Vachier, Isabelle
Assou, Said
Bourdin, Arnaud
De Vos, John
author_sort Ahmed, Engi
collection PubMed
description 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.
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spelling pubmed-93685292022-08-12 Differentiation of Human Induced Pluripotent Stem Cells from Patients with Severe COPD into Functional Airway Epithelium Ahmed, Engi Fieldes, Mathieu Bourguignon, Chloé Mianné, Joffrey Petit, Aurélie Jory, Myriam Cazevieille, Chantal Boukhaddaoui, Hassan Garnett, James P. Hirtz, Christophe Massiera, Gladys Vachier, Isabelle Assou, Said Bourdin, Arnaud De Vos, John Cells Article 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. MDPI 2022-08-05 /pmc/articles/PMC9368529/ /pubmed/35954266 http://dx.doi.org/10.3390/cells11152422 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ahmed, Engi
Fieldes, Mathieu
Bourguignon, Chloé
Mianné, Joffrey
Petit, Aurélie
Jory, Myriam
Cazevieille, Chantal
Boukhaddaoui, Hassan
Garnett, James P.
Hirtz, Christophe
Massiera, Gladys
Vachier, Isabelle
Assou, Said
Bourdin, Arnaud
De Vos, John
Differentiation of Human Induced Pluripotent Stem Cells from Patients with Severe COPD into Functional Airway Epithelium
title Differentiation of Human Induced Pluripotent Stem Cells from Patients with Severe COPD into Functional Airway Epithelium
title_full Differentiation of Human Induced Pluripotent Stem Cells from Patients with Severe COPD into Functional Airway Epithelium
title_fullStr Differentiation of Human Induced Pluripotent Stem Cells from Patients with Severe COPD into Functional Airway Epithelium
title_full_unstemmed Differentiation of Human Induced Pluripotent Stem Cells from Patients with Severe COPD into Functional Airway Epithelium
title_short Differentiation of Human Induced Pluripotent Stem Cells from Patients with Severe COPD into Functional Airway Epithelium
title_sort differentiation of human induced pluripotent stem cells from patients with severe copd into functional airway epithelium
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368529/
https://www.ncbi.nlm.nih.gov/pubmed/35954266
http://dx.doi.org/10.3390/cells11152422
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