A multimodal iPSC platform for cystic fibrosis drug testing.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 07 2022
29 07 2022
Historique:
received:
22
06
2021
accepted:
06
07
2022
entrez:
29
7
2022
pubmed:
30
7
2022
medline:
3
8
2022
Statut:
epublish
Résumé
Cystic fibrosis is a monogenic lung disease caused by dysfunction of the cystic fibrosis transmembrane conductance regulator anion channel, resulting in significant morbidity and mortality. The progress in elucidating the role of CFTR using established animal and cell-based models led to the recent discovery of effective modulators for most individuals with CF. However, a subset of individuals with CF do not respond to these modulators and there is an urgent need to develop novel therapeutic strategies. In this study, we generate a panel of airway epithelial cells using induced pluripotent stem cells from individuals with common or rare CFTR variants representative of three distinct classes of CFTR dysfunction. To measure CFTR function we adapt two established in vitro assays for use in induced pluripotent stem cell-derived airway cells. In both a 3-D spheroid assay using forskolin-induced swelling as well as planar cultures composed of polarized mucociliary airway epithelial cells, we detect genotype-specific differences in CFTR baseline function and response to CFTR modulators. These results demonstrate the potential of the human induced pluripotent stem cell platform as a research tool to study CF and in particular accelerate therapeutic development for CF caused by rare variants.
Identifiants
pubmed: 35906215
doi: 10.1038/s41467-022-31854-8
pii: 10.1038/s41467-022-31854-8
pmc: PMC9338271
doi:
Substances chimiques
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4270Subventions
Organisme : NHLBI NIH HHS
ID : F31 HL158197
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK065988
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM133364
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139799
Pays : United States
Informations de copyright
© 2022. The Author(s).
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