In vitro Methods for the Development and Analysis of Human Primary Airway Epithelia
Open accessAbstract
Cystic fibrosis (CF) is a chronic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, which encodes for a channel expressed at the apical surface of epithelial tissues. Defective chloride and bicarbonate secretion, arising from CFTR mutations, cause a multi-organ disease. In the airways, impaired ion transport results in a thick mucus, dehydration of the periciliar region and bacterial infections. Over the last years, basic research has sustained a great effort to identify therapies that are able to correct defective CFTR. For this purpose, in vitro cell models have played a key role in the study of mechanisms of the disease and to assess CFTR modulator therapies. Cultures of human primary bronchial epithelia are considered a physiologically relevant disease model due to their ability to maintain most of the morphological and functional characteristics of the airway epithelium in vivo. Despite their value, these cells are limited by the availability of human lung tissue and by the complexity of the culture procedure. However, primary human nasal cells can be considered as an alternative model for the study of CF pathophysiology since they are easier to obtain and recapitulate the properties of bronchial cultures. Over the years, several groups have optimized a protocol with key steps to culture and fully amplify differentiated primary airway epithelia. Our approach provides epithelia monolayers grown on porous filters, characterized by high transepithelial electrical resistance and an electrical potential difference. These parameters are required to perform electrophysiological experiments devoted to the study of ion transport mechanisms in airway epithelia. The aim of this study was to describe different methods to expand and differentiate isolated cells into fully polarized monolayers of airway epithelium, in order to provide an optimized protocol to support physiopathology analysis and to evaluate therapeutic strategies.
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Human primary airway epithelial cells are a physiologically relevant 2-D model for CF disease modeling and preclinical testing of CF therapies.
“Human primary airway epithelial cells are a physiologically relevant 2-D model for CF disease modeling and preclinical testing of CF therapies43,44.”
From Allele specific repair of splicing mutations in cystic fibrosis through AsCas12a genome editing (2019) · cites this paper as [44]
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- Authors
- Gianotti, A., Delpiano, L., & Caci, E.
- Affiliations
- Istituto Giannina Gaslini (IT)
- Corresponding author
- Caci, Emanuela
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2018-10-26
- Volume
- 9
- Pages
- 1176-1176
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC6212516
- OpenAlex
- W2894160627
- Cited by
- 38
- References
- 29
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 10 · 2020: 8 · 2019: 2
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- European Commission (HORIZON2020, 667079)
- Universidad Austral de Chile
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Keywords
- cystic fibrosis, CFTR, nasal epithelial cells, bronchial epithelial cells, epithelial monolayers, ion transport, CFTR modulator therapy, transepithelial electrical resistance, electrophysiology
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