| Title: |
Functional, Cohort-Level Assessment of CFTR Modulator Responses Using Biobanked Nasal Epithelial Cells from Individuals with Cystic Fibrosis |
| Authors: |
Aalbers, Bente L.; Amatngalim, Gimano D.; Aarts,Ellen M.; Rodenburg, Lisa W.; den Hertog-Oosterhoff, Loes A.; Heijerman, Harry G.M.; Beekman, Jeffrey M.; Onderzoek Longziekten; Cellular disease models 1; Child Health; Regenerative Medicine and Stem Cells; Genetica Oper.Mang. Clinical Genetics; Longziekten; Infection & Immunity; Algemeen management; Programmabureau Zorg van Morgen |
| Publication Year: |
2026 |
| Subject Terms: |
air-liquid interface (ALI) cultures; biobanking; cystic fibrosis; nasal epithelial cells; theratyping; Ussing chamber; Medicine (miscellaneous); Journal Article |
| Description: |
Background/Objectives: Individual responses to CFTR modulators vary widely among people with cystic fibrosis (pwCF), underscoring the need for functional approaches that provide biological context alongside genotype-based therapy selection. Nasal epithelial cultures provide an individual-specific model for theratyping, but most studies rely on freshly isolated cells, restricting repeated testing and long-term sample use. In this study, we tested whether CFTR modulator responses measured in biobanked nasal cells were associated with real-world clinical outcomes. Methods: Cryopreserved nasal epithelial cells from 23 pwCF were differentiated at the air–liquid interface and assessed for CFTR modulator-responsive ion transport using Ussing chambers. In vitro responses were correlated with 6-month changes in sweat chloride concentration (SCC), FEV1, and BMI. Results: Cryopreserved cultures retained donor-specific CFTR modulator responsiveness. Modulator-induced forskolin/IBMX-stimulated currents correlated with changes in SCC (R = −0.512). CFTR inhibitor-sensitive currents correlated with FEV1 (R = 0.564). Associations between forskolin/IBMX-stimulated currents and FEV1 were positive but did not reach statistical significance using two-tailed analysis. BMI changes showed no significant association. Conclusions: Biobanked nasal epithelial cultures preserve clinically relevant CFTR modulator responses at the cohort level, supporting their use as functional assays for population-level assessment in cystic fibrosis. This cryopreservation-based strategy enables repeated testing and may expand access to theratyping beyond freshly obtained samples. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
2075-4426 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/469326 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/469326 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.1212AFA6 |
| Database: |
BASE |