{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T15:57:31Z","timestamp":1768665451463,"version":"3.49.0"},"reference-count":22,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016032","name":"Dutch Cystic Fibrosis Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016032","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001826","name":"the Netherlands Organization for Health Research and Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Health Holland","award":["40-41200-98-9296"],"award-info":[{"award-number":["40-41200-98-9296"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>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\u2013liquid 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 = \u22120.512). 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.<\/jats:p>","DOI":"10.3390\/jpm16010051","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:13:21Z","timestamp":1768475601000},"page":"51","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional, Cohort-Level Assessment of CFTR Modulator Responses Using Biobanked Nasal Epithelial Cells from Individuals with Cystic Fibrosis"],"prefix":"10.3390","volume":"16","author":[{"given":"Bente L.","family":"Aalbers","sequence":"first","affiliation":[{"name":"Department of Pulmonology, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3442-1754","authenticated-orcid":false,"given":"Gimano D.","family":"Amatngalim","sequence":"additional","affiliation":[{"name":"Lab of Cellular Disease Models, Department of Pediatrics, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8714-061X","authenticated-orcid":false,"given":"Ellen M.","family":"Aarts","sequence":"additional","affiliation":[{"name":"Lab of Cellular Disease Models, Department of Pediatrics, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8113-4304","authenticated-orcid":false,"given":"Lisa W.","family":"Rodenburg","sequence":"additional","affiliation":[{"name":"Lab of Cellular Disease Models, Department of Pediatrics, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loes A.","family":"den Hertog-Oosterhoff","sequence":"additional","affiliation":[{"name":"Lab of Cellular Disease Models, Department of Pediatrics, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry G. M.","family":"Heijerman","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey M.","family":"Beekman","sequence":"additional","affiliation":[{"name":"Lab of Cellular Disease Models, Department of Pediatrics, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands"},{"name":"Centre for Living Technologies, Alliance Eindhoven University of Technology, Wageningen University & Research, University Medical Center Utrecht, Utrecht University, 3584 CB Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1016\/S0140-6736(16)00576-6","article-title":"Cystic Fibrosis","volume":"388","author":"Elborn","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41467-023-36244-2","article-title":"Future therapies for cystic fibrosis","volume":"14","author":"Allen","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"00204","DOI":"10.1183\/23120541.00204-2022","article-title":"Dutch Cystic Fibrosis Registry (NCFR) Steering Group: Long-term effectiveness of dual CFTR modulator treatment of cystic fibrosis","volume":"8","author":"Muilwijk","year":"2022","journal-title":"ERJ Open Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jcf.2018.05.004","article-title":"CFTR modulator theratyping: Current status, gaps and future directions","volume":"18","author":"Clancy","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Keegan, D.E., and Brewington, J.J. (2021). Nasal Epithelial Cell-Based Models for Individualized Study in Cystic Fibrosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094448"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e99385","DOI":"10.1172\/jci.insight.99385","article-title":"Brushed nasal epithelial cells are a surrogate for bronchial epithelial CFTR studies","volume":"3","author":"Brewington","year":"2018","journal-title":"JCI Insight"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.15252\/emmm.201607137","article-title":"Orkambi\u00ae and amplifier co-therapy improves function from a rare CFTR mutation in gene-edited cells and patient tissue","volume":"9","author":"Molinski","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1702457","DOI":"10.1183\/13993003.02457-2017","article-title":"Personalised CFTR pharmacotherapeutic response testing and therapy of cystic fibrosis","volume":"51","author":"McCarthy","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Veit, G., Velkov, T., Xu, H., Vadeboncoeur, N., Bilodeau, L., Matouk, E., and Lukacs, G.L. (2021). A precision medicine approach to optimize modulator therapy for rare CFTR folding mutants. J. Pers. Med., 11.","DOI":"10.3390\/jpm11070643"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7375","DOI":"10.1038\/s41598-017-07504-1","article-title":"Correction of CFTR function in nasal epithelial cells from cystic fibrosis patients predicts improvement of respiratory function by CFTR modulators","volume":"7","author":"Pranke","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1164\/rccm.201808-1436LE","article-title":"Might brushed nasal cells be a surrogate for CFTR modulator clinical response?","volume":"199","author":"Pranke","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2100908","DOI":"10.1183\/13993003.00908-2021","article-title":"Theratyping cystic fibrosis in vitro in ALI culture and organoid models generated from patient-derived nasal epithelial conditionally reprogrammed stem cells","volume":"58","author":"Sette","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1113\/JP282143","article-title":"Correlating genotype with phenotype using CFTR-mediated whole-cell Cl- currents in human nasal epithelial cells","volume":"600","author":"Noel","year":"2022","journal-title":"J. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2401855","DOI":"10.1183\/13993003.01855-2024","article-title":"Relationship between theratyping in nasal epithelial cells and clinical outcomes in people with cystic fibrosis","volume":"65","author":"Ratjen","year":"2025","journal-title":"Eur. Respir. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e202101320","DOI":"10.26508\/lsa.202101320","article-title":"Measuring cystic fibrosis drug responses in organoids derived from 2D differentiated nasal epithelia","volume":"5","author":"Amatngalim","year":"2022","journal-title":"Life Sci. Alliance"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102337","DOI":"10.1016\/j.xpro.2023.102337","article-title":"Protocol for generating airway organoids from 2D air liquid interface-differentiated nasal epithelia for use in a functional CFTR assay","volume":"4","author":"Rodenburg","year":"2023","journal-title":"STAR Protoc."},{"key":"ref_17","first-page":"e63409","article-title":"Primary human nasal epithelial cells: Biobanking in the context of precision medicine","volume":"182","author":"Kelly","year":"2022","journal-title":"J. Vis. Exp."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2300110","DOI":"10.1183\/13993003.00110-2023","article-title":"Theratyping cystic fibrosis patients to guide elexacaftor\/tezacaftor\/ivacaftor out-of-label prescription","volume":"62","author":"Dreano","year":"2023","journal-title":"Eur. Respir. J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Park, J.K., Shrivastava, A., Zhang, C., Pollok, B.A., Finkbeiner, W.E., Gibb, E.R., Ly, N.P., and Illek, B. (2020). Functional Profiling of CFTR-Directed Therapeutics Using Pediatric Patient-Derived Nasal Epithelial Cell Models. Front. Pediatr., 8.","DOI":"10.3389\/fped.2020.00536"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Saint-Criq, V., Delpiano, L., Casement, J., Onuora, J.C., Lin, J., and Gray, M.A. (2020). Choice of differentiation media significantly impacts cell lineage and response to CFTR modulators in fully differentiated primary cultures of cystic fibrosis human airway epithelial cells. Cells, 9.","DOI":"10.3390\/cells9092137"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e14603","DOI":"10.14814\/phy2.14603","article-title":"Effect of apical chloride concentration on the measurement of responses to CFTR modulation in airway epithelia cultured from nasal brushings","volume":"8","author":"Bratcher","year":"2020","journal-title":"Physiol. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1016\/j.celrep.2019.01.068","article-title":"Rectal organoids enable personalized treatment of cystic fibrosis","volume":"26","author":"Berkers","year":"2019","journal-title":"Cell Rep."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/1\/51\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T05:34:45Z","timestamp":1768628085000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/1\/51"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,15]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["jpm16010051"],"URL":"https:\/\/doi.org\/10.3390\/jpm16010051","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,15]]}}}