{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:55:47Z","timestamp":1781769347753,"version":"3.54.5"},"reference-count":97,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation for the Research Centre for Medical Genetics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cystic fibrosis (CF) is a genetic disorder caused by dysfunction of the CFTR chloride ion channel. Progress in molecular understanding and therapy development relies on advanced cellular models and robust assays for evaluating CFTR function. This review traces the evolution of in vitro models, from primary and immortalized cell lines to patient-specific induced pluripotent stem cells (iPSCs) and complex three-dimensional systems. These advanced models, including air-liquid interface (ALI) cultures, organoids, and microfluidic organ-on-a-chip platforms, enable recapitulation of tissue architecture, cellular heterogeneity, and key pathological features such as impaired mucociliary clearance and chronic inflammation. A critical component of CF research is the accurate functional assessment of CFTR activity. We compare established high-resolution techniques (patch-clamp, Ussing chamber) with high-throughput screening assays, including fluorescence quenching of halide-sensitive YFP assay and organoid swelling tests. The article provides a framework for choosing the most appropriate CFTR functional assay tailored to specific research goals.<\/jats:p>","DOI":"10.3390\/ijms27125497","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:33:54Z","timestamp":1781768034000},"page":"5497","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cellular Models and Functional Assays for Assessing CFTR Function: A Comprehensive Review"],"prefix":"10.3390","volume":"27","author":[{"given":"Margarita","family":"Lopatina","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye, 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4460-7627","authenticated-orcid":false,"given":"Anna","family":"Demchenko","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye, 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Smirnikhina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye, 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nrg3849","article-title":"Cystic fibrosis genetics: From molecular understanding to clinical application","volume":"16","author":"Cutting","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"171","DOI":"10.18093\/0869-0189-2023-33-2-171-181","article-title":"Russian registry of patients with cystic fibrosis: Lessons and perspectives","volume":"33","author":"Kondratyeva","year":"2023","journal-title":"Pulmonologiya"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s00018-016-2386-8","article-title":"The cystic fibrosis transmembrane conductance regulator (CFTR) and its stability","volume":"74","author":"Meng","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1042\/BST20180296","article-title":"The structural basis of cystic fibrosis","volume":"46","author":"Meng","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Bacalhau, M., Ferreira, F.C., Silva, I.A.L., Buarque, C.D., Amaral, M.D., and Lopes-Pacheco, M. (2023). Additive potentiation of R334W-CFTR function by novel small molecules. J. Pers. Med., 13.","DOI":"10.3390\/jpm13010102"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1134\/S1022795418100022","article-title":"Updating diagnostic spectrum of recurring CFTR mutations","volume":"54","author":"Adyan","year":"2018","journal-title":"Russ. J. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e165","DOI":"10.1016\/j.lpm.2017.01.024","article-title":"New treatments targeting the basic defects in cystic fibrosis","volume":"46","author":"Fajac","year":"2017","journal-title":"Presse Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1007\/s00108-020-00896-9","article-title":"Was ist gesichert in der Therapie der Mukoviszidose?","volume":"61","author":"Ringshausen","year":"2020","journal-title":"Internist"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Bergeron, C., and Cantin, A.M. (2021). New therapies to correct the cystic fibrosis basic defect. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126193"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"118325","DOI":"10.1016\/j.ejmech.2025.118325","article-title":"Modulators of anion channels and transporters as alternative therapeutic agents to normalize airway surface liquid in cystic fibrosis","volume":"302","author":"Lipani","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.psym.2017.04.001","article-title":"Cystic fibrosis transmembrane regulator modulators: Implications for the management of depression and anxiety in cystic fibrosis","volume":"58","author":"Talwalkar","year":"2017","journal-title":"Psychosomatics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1111\/jcpt.13329","article-title":"A current review of the safety of cystic fibrosis transmembrane conductance regulator modulators","volume":"46","author":"Gavioli","year":"2021","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Plasschaert, L.W., MacDonald, K.D., and Moffit, J.S. (2024). Current landscape of cystic fibrosis gene therapy. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1476331"},{"key":"ref_14","first-page":"3","article-title":"Intestinal organoids and their application for personalized diagnostics and treatment of cystic fibrosis","volume":"17","author":"Efremova","year":"2018","journal-title":"Med. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1165\/rcmb.2012-0419RC","article-title":"Cystic fibrosis transmembrane conductance regulator is expressed in mucin granules from Calu-3 and primary human airway epithelial cells","volume":"49","author":"LeSimple","year":"2013","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1126\/science.6308769","article-title":"Abnormal ion permeation through cystic fibrosis respiratory epithelium","volume":"221","author":"Knowles","year":"1983","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"18825","DOI":"10.1073\/pnas.0904709106","article-title":"Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770","volume":"106","author":"Hadida","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.jcf.2024.02.006","article-title":"In vitro modulator responsiveness of 655 CFTR variants found in people with cystic fibrosis","volume":"23","author":"Bihler","year":"2024","journal-title":"J. Cyst. Fibros."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.yexmp.2009.09.018","article-title":"CFTR and tight junctions in cultured bronchial epithelial cells","volume":"88","author":"Nilsson","year":"2010","journal-title":"Exp. Mol. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Smirnikhina, S.A., Kondrateva, E.V., Adilgereeva, E.P., Anuchina, A.A., Zaynitdinova, M.I., Slesarenko, Y.S., Ershova, A.S., Ustinov, K.D., Yasinovsky, M.I., and Amelina, E.L.P. (2020). F508del editing in cells from cystic fibrosis patients. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0242094"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.1038\/s41467-022-31854-8","article-title":"A multimodal iPSC platform for cystic fibrosis drug testing","volume":"13","author":"Berical","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jcf.2017.06.010","article-title":"Detection of CFTR function and modulation in primary human nasal cell spheroids","volume":"17","author":"Brewington","year":"2018","journal-title":"J. Cyst. Fibros."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1186\/s12931-020-01486-x","article-title":"Flagellin shifts 3D bronchospheres towards mucus hyperproduction","volume":"21","author":"Sprott","year":"2020","journal-title":"Respir. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.celrep.2014.12.017","article-title":"Notch2 is required for inflammatory cytokine-driven goblet cell metaplasia in the lung","volume":"10","author":"Danahay","year":"2015","journal-title":"Cell Rep."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Liu, Z., Anderson, J.D., Deng, L., Mackay, S., Bailey, J., Kersh, L., Rowe, S.M., and Guimbellot, J.S. (2020). Human nasal epithelial organoids for therapeutic development in cystic fibrosis. Genes, 11.","DOI":"10.3390\/genes11060603"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/nm.3201","article-title":"A functional CFTR assay using primary cystic fibrosis intestinal organoids","volume":"19","author":"Dekkers","year":"2013","journal-title":"Nat. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"43321","DOI":"10.1038\/srep43321","article-title":"Antimicrobial efficacy against Pseudomonas aeruginosa biofilm formation in a three-dimensional lung epithelial model and the influence of fetal bovine serum","volume":"7","author":"Liu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100013","DOI":"10.1016\/j.celbio.2025.100013","article-title":"Development of a 3D bioengineered human lung submucosal gland ductal airway model to study mucociliary clearance in vitro","volume":"1","author":"Kim","year":"2025","journal-title":"Cell Biomater."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"332","DOI":"10.18063\/ijb.v7i2.332","article-title":"Fabrication and characterization of 3D bioprinted triple-layered human alveolar lung models","volume":"7","author":"Ng","year":"2021","journal-title":"Int. J. Bioprinting"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1021\/acsbiomaterials.2c01460","article-title":"Easy-to-Build and reusable microfluidic device for the dynamic culture of human bronchial cystic fibrosis epithelia","volume":"9","author":"Mazio","year":"2023","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3601","DOI":"10.1039\/D0LC00644K","article-title":"A 96-well format microvascularized human lung-on-a-chip platform for microphysiological modeling of fibrotic diseases","volume":"20","author":"Nelson","year":"2020","journal-title":"Lab A Chip"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.jcf.2021.10.004","article-title":"Modeling pulmonary cystic fibrosis in a human lung airway-on-a-chip","volume":"21","author":"Plebani","year":"2022","journal-title":"J. Cyst. Fibros."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1038\/s41467-021-22676-1","article-title":"Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week","volume":"12","author":"Hu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jcf.2018.05.004","article-title":"WallenburgCFTR modulator theratyping: Current status, gaps and future directions","volume":"18","author":"Clancy","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mad\u00e1csy, T., Pallagi, P., and Maleth, J. (2018). Cystic fibrosis of the pancreas: The role of CFTR channel in the regulation of intracellular Ca2+ signaling and mitochondrial function in the exocrine pancreas. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.01585"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/s41598-018-36735-z","article-title":"Optimization of normal human bronchial epithelial (NHBE) cell 3D cultures for in vitro lung model studies","volume":"9","author":"Rayner","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s00441-005-0062-7","article-title":"Towards an in vitro model of cystic fibrosis small airway epithelium: Characterisation of the human bronchial epithelial cell line CFBE41o","volume":"323","author":"Ehrhardt","year":"2006","journal-title":"Cell Tissue Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jcf.2004.05.040","article-title":"Established cell lines used in cystic fibrosis research","volume":"3","author":"Gruenert","year":"2004","journal-title":"J. Cyst. Fibros."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3109\/01902140903165265","article-title":"Primary bronchial epithelial cell culture from explanted cystic fibrosis lungs","volume":"36","author":"Brodlie","year":"2010","journal-title":"Exp. Lung Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Cheng, W., Fan, C., Song, Q., Chen, P., Peng, H., Lin, L., Liu, C., Wang, B., and Zhou, Z. (2023). Induced pluripotent stem cell-based therapies for organ fibrosis. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1119606"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.celrep.2015.07.062","article-title":"Functional gene correction for cystic fibrosis in lung epithelial cells generated from patient iPSCs","volume":"12","author":"Firth","year":"2015","journal-title":"Cell Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/j.omtm.2020.04.005","article-title":"iPSC-derived intestinal organoids from cystic fibrosis patients acquire CFTR activity upon TALEN-mediated repair of the p. F508del mutation","volume":"17","author":"Fleischer","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.stem.2013.11.002","article-title":"Functional repair of CFTR by CRISPR\/Cas9 in intestinal stem cell organoids of cystic fibrosis patients","volume":"13","author":"Schwank","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1038\/nbt.2328","article-title":"Directed differentiation of human pluripotent stem cells into mature airway epithelia expressing functional CFTR protein","volume":"30","author":"Wong","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1007\/s12015-024-10776-6","article-title":"Progesterone receptor is constitutively expressed in induced Pluripotent Stem Cells (iPSCs)","volume":"20","author":"Manganelli","year":"2024","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1165\/rcmb.2008-0018OC","article-title":"Functional properties of mixed cystic fibrosis and normal bronchial epithelial cell cultures","volume":"40","author":"Dannhoffer","year":"2009","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1159\/000324011","article-title":"Sensitivity of chloride efflux vs. transepithelial measurements in mixed CF and normal airway epithelial cell populations","volume":"26","author":"Illek","year":"2011","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5382","DOI":"10.1073\/pnas.1604905113","article-title":"Relationships among CFTR expression, HCO3\u2212 secretion, and host defense may inform gene-and cell-based cystic fibrosis therapies","volume":"113","author":"Shah","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","first-page":"170","article-title":"Course of the disease with evaluation of the chloride channel function and selection of target therapy in vitro in an adult with cystic fibrosis with 2184insa\/l138ins genotype","volume":"15","author":"Melyanovskaya","year":"2020","journal-title":"Med. News North Cauc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s41231-020-00060-3","article-title":"Rationale and design of the HIT-CF organoid study: Stratifying cystic fibrosis patients based on intestinal organoid response to different CFTR-modulators","volume":"5","author":"Michel","year":"2020","journal-title":"Transl. Med. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ramalho, A.S., Boon, M., Proesmans, M., Vermeulen, F., Carlon, M.S., and De Boeck, K. (2022). Assays of CFTR function in vitro, ex vivo and in vivo. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031437"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"L119","DOI":"10.1152\/ajplung.00639.2020","article-title":"CFTR function and clinical response to modulators parallel nasal epithelial organoid swelling","volume":"321","author":"Anderson","year":"2021","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Demchenko, A., Balyasin, M., Nazarova, A., Grigorieva, O., Panchuk, I., Kondrateva, E., Tabakov, V., Schagina, O., Amelina, E., and Smirnikhina, S. (2025). Human induced lung organoids: A promising tool for cystic fibrosis drug screening. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26020437"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Rodenburg, L.W., Delpiano, L., Railean, V., Centeio, R., Pinto, M.C., Smits, S.M., van der Windt, I.S., van Hugten, C.F.J., van Beuningen, S.F.B., and Rodenburg, R.N.P. (2022). Drug repurposing for cystic fibrosis: Identification of drugs that induce CFTR-independent fluid secretion in nasal organoids. Int. J. Mol. Sci., 23.","DOI":"10.1101\/2022.09.23.509034"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lefferts, J.W., Bierlaagh, M.C., Kroes, S., Nieuwenhuijze, N.D., Sonneveld van Kooten, H.N., Niem\u00f6ller, P.J., Verburg, T.F., Janssens, H.M., Muilwijk, D., and van Beuningen, S.F.B. (2023). CFTR function restoration upon elexacaftor\/tezacaftor\/ivacaftor treatment in patient-derived intestinal organoids with rare CFTR genotypes. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914539"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"102148","DOI":"10.1016\/j.mtbio.2025.102148","article-title":"Organoid-on-a-chip (OrgOC): Advancing cystic fibrosis research","volume":"34","author":"Zheng","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Li, Z., Hui, J., Yang, P., and Mao, H. (2022). Microfluidic organ-on-a-chip system for disease modeling and drug development. Biosensors, 12.","DOI":"10.3390\/bios12060370"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.jcf.2008.05.003","article-title":"On the measurement of the functional properties of the CFTR","volume":"7","author":"Moran","year":"2008","journal-title":"J. Cyst. Fibros."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"MSB202110629","DOI":"10.15252\/msb.202110629","article-title":"CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system","volume":"18","author":"Lim","year":"2022","journal-title":"Mol. Syst. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/s41586-023-05854-7","article-title":"CFTR function, pathology and pharmacology at single-molecule resolution","volume":"616","author":"Levring","year":"2023","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1136\/thx.2009.125088","article-title":"Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: Validation and reference data","volume":"65","author":"Derichs","year":"2010","journal-title":"Thorax"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1089\/10430349950018274","article-title":"Fluorescent chloride indicators to assess the efficacy of CFTR cDNA delivery","volume":"10","author":"Mansoura","year":"1999","journal-title":"Hum. Gene Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S0014-5793(01)02561-3","article-title":"Green fluorescent protein-based halide indicators with improved chloride and iodide affinities","volume":"499","author":"Galietta","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6047","DOI":"10.1074\/jbc.275.9.6047","article-title":"Mechanism and cellular applications of a green fluorescent protein-based halide sensor","volume":"275","author":"Jayaraman","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e95734","DOI":"10.1172\/jci.insight.95734","article-title":"Nasospheroids permit measurements of CFTR-dependent fluid transport","volume":"2","author":"Guimbellot","year":"2017","journal-title":"JCI Insight"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.jcf.2022.01.008","article-title":"Forskolin induced swelling (FIS) assay in intestinal organoids to guide eligibility for compassionate use treatment in a CF patient with a rare genotype","volume":"21","author":"Aalbers","year":"2022","journal-title":"J. Cyst. Fibros."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"50","DOI":"10.20953\/1817-7646-2018-4-50-64","article-title":"Functional methods of diagnosing disorders of the CFTR gene and its product","volume":"13","author":"Kondratyeva","year":"2018","journal-title":"Vopr. Prakt. Pediatr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1802379","DOI":"10.1183\/13993003.02379-2018","article-title":"Intestinal organoids to model cystic fibrosis","volume":"54","author":"Beekman","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Billet, A., Froux, L., Hanrahan, J.W., and Becq, F. (2017). Development of automated patch clamp technique to investigate CFTR chloride channel function. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00195"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2100671","DOI":"10.1183\/13993003.00671-2021","article-title":"The rescue of F508del-CFTR by elexacaftor\/tezacaftor\/ivacaftor (Trikafta) in human airway epithelial cells is underestimated due to the presence of ivacaftor","volume":"59","author":"Becq","year":"2022","journal-title":"Eur. Respir. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jcf.2004.05.046","article-title":"The patch-clamp and planar lipid bilayer techniques: Powerful and versatile tools to investigate the CFTR Cl\u2212 channel","volume":"3","author":"Sheppard","year":"2004","journal-title":"J. Cyst. Fibros."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1113\/JP282143","article-title":"Correlating genotype with phenotype using CFTR-mediated whole-cell Cl\u2212 currents in human nasal epithelial cells","volume":"600","author":"Noel","year":"2022","journal-title":"J. Physiol."},{"key":"ref_73","unstructured":"Scott-Ward, T.S., Chen, J.H., Li, H., Cai, Z., and Sheppard, D.N. (2003). Investigating the CFTR Cl-channel using the patch-clamp technique: An overview. Virtual Repos."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"22616","DOI":"10.1038\/s41598-021-02044-1","article-title":"Measurements of spontaneous CFTR-mediated ion transport without acute channel activation in airway epithelial cultures after modulator exposure","volume":"11","author":"Nick","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"18843","DOI":"10.1073\/pnas.1105787108","article-title":"Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809","volume":"108","author":"Hadida","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1080\/17460441.2020.1750592","article-title":"The preclinical discovery and development of the combination of ivacaftor+ tezacaftor used to treat cystic fibrosis","volume":"15","author":"Guerra","year":"2020","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.ymthe.2021.03.023","article-title":"Targeted replacement of full-length CFTR in human airway stem cells by CRISPR-Cas9 for pan-mutation correction in the endogenous locus","volume":"30","author":"Vaidyanathan","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"L313","DOI":"10.1152\/ajplung.00137.2024","article-title":"Toward in vivo bronchoscopic functional CFTR assessment using a short circuit current measurement probe","volume":"328","author":"Otuya","year":"2025","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.jcf.2020.12.019","article-title":"Significant functional differences in differentiated Conditionally Reprogrammed (CRC)-and Feeder-free Dual SMAD inhibited-expanded human nasal epithelial cells","volume":"20","author":"Awatade","year":"2021","journal-title":"J. Cyst. Fibros."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1023\/A:1009766219974","article-title":"Iodide efflux measurements with an iodide-selective electrode: A non-radioactive procedure for monitoring cellular chloride transport","volume":"19","author":"Long","year":"1997","journal-title":"Methods Cell Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"L832","DOI":"10.1152\/ajplung.00287.2024","article-title":"Lumacaftor inhibits channel activity of rescued F508del cystic fibrosis transmembrane conductance regulator","volume":"328","author":"Ambrosetti","year":"2025","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_82","first-page":"100863","article-title":"Is CFTR an exchanger?: Regulation of HCO3\u2212 Transport and extracellular pH by CFTR","volume":"25","author":"Massey","year":"2021","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_83","unstructured":"Dada, M.A. (2025). Effect of CFTR Modulators on Chloride Homeostasis and Excitability in Sensory Neurons from CFTR F508del Mice. [Master\u2019s Thesis, University of Saskatchewan]."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.ab.2011.07.029","article-title":"Measurement of cystic fibrosis transmembrane conductance regulator activity using fluorescence spectrophotometry","volume":"418","author":"Valdivieso","year":"2011","journal-title":"Anal. Biochem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"C1734","DOI":"10.1152\/ajpcell.2001.281.5.C1734","article-title":"Cell-based assay for high-throughput quantitative screening of CFTR chloride transport agonists","volume":"281","author":"Galietta","year":"2001","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1111\/bph.13715","article-title":"Improved fluorescence assays to measure the defects associated with F508del-CFTR allow identification of new active compounds","volume":"174","author":"Langron","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1","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_88","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s42003-024-05966-4","article-title":"OrgaSegment: Deep-learning based organoid segmentation to quantify CFTR dependent fluid secretion","volume":"7","author":"Lefferts","year":"2024","journal-title":"Commun. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Rodriguez Mier, N., Destoop, M., Spelier, S., Ramalho, A.S., Beekman, J.M., Vermeulen, F., de Winter-de Groot, K.M., and Proesmans, M. (2025). The Promising Role of Intestinal Organoids in the Diagnostic Work-Up of Cystic Fibrosis Screen Positive Inconclusive Diagnosis\/CFTR-Related Metabolic Syndrome (CFSPID\/CRMS). Int. J. Neonatal Screen., 11.","DOI":"10.3390\/ijns11030052"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Conti, J., Sorio, C., and Melotti, P. (2022). Organoid technology and its role for theratyping applications in cystic fibrosis. Children, 10.","DOI":"10.3390\/children10010004"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"344ra84","DOI":"10.1126\/scitranslmed.aad8278","article-title":"Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis","volume":"8","author":"Dekkers","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5686","DOI":"10.1093\/bioinformatics\/btaa1073","article-title":"An open-source high-content analysis workflow for CFTR function measurements using the forskolin-induced swelling assay","volume":"36","author":"Hagemeijer","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.jcf.2024.04.014","article-title":"Repeatability and reproducibility of the Forskolin-induced swelling (FIS) assay on intestinal organoids from people with Cystic Fibrosis","volume":"23","author":"Bierlaagh","year":"2024","journal-title":"J. Cyst. Fibros."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"100019","DOI":"10.1016\/j.xpro.2020.100019","article-title":"Protocol for application, standardization and validation of the forskolin-induced swelling assay in cystic fibrosis human colon organoids","volume":"1","author":"Vonk","year":"2020","journal-title":"STAR Protoc."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"L1117","DOI":"10.1152\/ajplung.00169.2005","article-title":"Rescue of \u0394F508-CFTR trafficking and gating in human cystic fibrosis airway primary cultures by small molecules","volume":"290","author":"Straley","year":"2006","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1172\/JCI24898","article-title":"Small-molecule correctors of defective \u0394F508-CFTR cellular processing identified by high-throughput screening","volume":"115","author":"Pedemonte","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.jcf.2019.06.010","article-title":"Theranostics by testing CFTR modulators in patient-derived materials: The current status and a proposal for subjects with rare CFTR mutations","volume":"18","author":"Amaral","year":"2019","journal-title":"J. Cyst. Fibros."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5497\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:35:20Z","timestamp":1781768120000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,18]]},"references-count":97,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125497"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125497","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,18]]}}}