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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9368529 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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