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Human Primary Epithelial Cell Models: Promising Tools in the Era of Cystic Fibrosis Personalized Medicine

Cystic fibrosis (CF) is an inherited disorder where individual disease etiology and response to therapeutic intervention is impacted by CF transmembrane regulator (CFTR) mutations and other genetic modifiers. CFTR regulates multiple mechanisms in a diverse range of epithelial tissues. In this Review...

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Autores principales: Awatade, Nikhil T., Wong, Sharon L., Hewson, Chris K., Fawcett, Laura K., Kicic, Anthony, Jaffe, Adam, Waters, Shafagh A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293199/
https://www.ncbi.nlm.nih.gov/pubmed/30581387
http://dx.doi.org/10.3389/fphar.2018.01429
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author Awatade, Nikhil T.
Wong, Sharon L.
Hewson, Chris K.
Fawcett, Laura K.
Kicic, Anthony
Jaffe, Adam
Waters, Shafagh A.
author_facet Awatade, Nikhil T.
Wong, Sharon L.
Hewson, Chris K.
Fawcett, Laura K.
Kicic, Anthony
Jaffe, Adam
Waters, Shafagh A.
author_sort Awatade, Nikhil T.
collection PubMed
description Cystic fibrosis (CF) is an inherited disorder where individual disease etiology and response to therapeutic intervention is impacted by CF transmembrane regulator (CFTR) mutations and other genetic modifiers. CFTR regulates multiple mechanisms in a diverse range of epithelial tissues. In this Review, we consolidate the latest updates in the development of primary epithelial cellular model systems relevant for CF. We discuss conventional two-dimensional (2-D) airway epithelial cell cultures, the backbone of in vitro cellular models to date, as well as improved expansion protocols to overcome finite supply of the cellular source. We highlight a range of strategies for establishment of three dimensional (3-D) airway and intestinal organoid models and evaluate the limitations and potential improvements in each system, focusing on their application in CF. The in vitro CFTR functional assays in patient-derived organoids allow for preclinical pharmacotherapy screening to identify responsive patients. It is likely that organoids will be an invaluable preclinical tool to unravel disease mechanisms, design novel treatments, and enable clinicians to provide personalized management for patients with CF.
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spelling pubmed-62931992018-12-21 Human Primary Epithelial Cell Models: Promising Tools in the Era of Cystic Fibrosis Personalized Medicine Awatade, Nikhil T. Wong, Sharon L. Hewson, Chris K. Fawcett, Laura K. Kicic, Anthony Jaffe, Adam Waters, Shafagh A. Front Pharmacol Pharmacology Cystic fibrosis (CF) is an inherited disorder where individual disease etiology and response to therapeutic intervention is impacted by CF transmembrane regulator (CFTR) mutations and other genetic modifiers. CFTR regulates multiple mechanisms in a diverse range of epithelial tissues. In this Review, we consolidate the latest updates in the development of primary epithelial cellular model systems relevant for CF. We discuss conventional two-dimensional (2-D) airway epithelial cell cultures, the backbone of in vitro cellular models to date, as well as improved expansion protocols to overcome finite supply of the cellular source. We highlight a range of strategies for establishment of three dimensional (3-D) airway and intestinal organoid models and evaluate the limitations and potential improvements in each system, focusing on their application in CF. The in vitro CFTR functional assays in patient-derived organoids allow for preclinical pharmacotherapy screening to identify responsive patients. It is likely that organoids will be an invaluable preclinical tool to unravel disease mechanisms, design novel treatments, and enable clinicians to provide personalized management for patients with CF. Frontiers Media S.A. 2018-12-07 /pmc/articles/PMC6293199/ /pubmed/30581387 http://dx.doi.org/10.3389/fphar.2018.01429 Text en Copyright © 2018 Awatade, Wong, Hewson, Fawcett, Kicic, Jaffe and Waters. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Awatade, Nikhil T.
Wong, Sharon L.
Hewson, Chris K.
Fawcett, Laura K.
Kicic, Anthony
Jaffe, Adam
Waters, Shafagh A.
Human Primary Epithelial Cell Models: Promising Tools in the Era of Cystic Fibrosis Personalized Medicine
title Human Primary Epithelial Cell Models: Promising Tools in the Era of Cystic Fibrosis Personalized Medicine
title_full Human Primary Epithelial Cell Models: Promising Tools in the Era of Cystic Fibrosis Personalized Medicine
title_fullStr Human Primary Epithelial Cell Models: Promising Tools in the Era of Cystic Fibrosis Personalized Medicine
title_full_unstemmed Human Primary Epithelial Cell Models: Promising Tools in the Era of Cystic Fibrosis Personalized Medicine
title_short Human Primary Epithelial Cell Models: Promising Tools in the Era of Cystic Fibrosis Personalized Medicine
title_sort human primary epithelial cell models: promising tools in the era of cystic fibrosis personalized medicine
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293199/
https://www.ncbi.nlm.nih.gov/pubmed/30581387
http://dx.doi.org/10.3389/fphar.2018.01429
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