Correction of CFTR function in intestinal organoids to guide treatment of cystic fibrosis
Open accessAbstract
Rationale: Given the vast number of cystic fibrosis transmembrane conductance regulator ( CFTR ) mutations, biomarkers predicting benefit from CFTR modulator therapies are needed for subjects with cystic fibrosis (CF). Objectives: To study CFTR function in organoids of subjects with common and rare CFTR mutations and evaluate correlations between CFTR function and clinical data. Methods: Intestinal organoids were grown from rectal biopsies in a cohort of 97 subjects with CF. Residual CFTR function was measured by quantifying organoid swelling induced by forskolin and response to modulators by quantifying organoid swelling induced by CFTR correctors, potentiator and their combination. Organoid data were correlated with clinical data from the literature. Results: Across 28 genotypes, residual CFTR function correlated (r 2 =0.87) with sweat chloride values. When studying the same genotypes, CFTR function rescue by CFTR modulators in organoids correlated tightly with mean improvement in lung function (r 2 =0.90) and sweat chloride (r 2 =0.95) reported in clinical trials. We identified candidate genotypes for modulator therapy, such as E92K, Q237E, R334W and L159S. Based on organoid results, two subjects started modulator treatment: one homozygous for complex allele Q359K_T360K, and the second with mutation E60K. Both subjects had major clinical benefit. Conclusions: Measurements of residual CFTR function and rescue of function by CFTR modulators in intestinal organoids correlate closely with clinical data. Our results for reference genotypes concur with previous results. CFTR function measured in organoids can be used to guide precision medicine in patients with CF, positioning organoids as a potential in vitro model to bring treatment to patients carrying rare CFTR mutations.
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Living biobanks can provide access to patient-derived cells and organoids from large patient cohorts, and have already been established for different cancers, genetic diseases such as cystic fibrosis, infectious diseases, chronic obstructive pulmonary disease and inflammatory bowel diseases.
“‘living biobanks’ can provide access to patient-derived cells and organoids from large patient cohorts, and have already been established for different cancers124,151,176–178, genetic diseases such as cystic fibrosis, infectious diseases, chronic obstructive pulmonary disease and inflammatory bowel diseases179”
From Human disease models in drug development (2023) · cites this paper as [179]
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CFTR function and clinical response to modulators parallel nasal epithelial organoid swelling
Anderson, J. D., Liu, Z., Odom, L. V., Kersh, L., & Guimbellot, J. S. (2021) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00639.2020 · Cited by 28 · see citing works
Silva, I. A. L., Railean, V., Duarte, A., & Amaral, M. D. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11050421 · Cited by 28 · see citing works
On the Corner of Models and Cure: Gene Editing in Cystic Fibrosis
Ensinck, M. M., Mottais, A., Detry, C., Leal, T., & Carlon, M. S. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.662110 · Cited by 28 · see citing works
Basic and Preclinical Research for Personalized Medicine
Lattanzi, W., Ripoli, C., Greco, V., Barba, M., Iavarone, F., Minucci, A., Urbani, A., Grassi, C., & Parolini, O. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11050354 · Cited by 29 · see citing works
Kondratyeva, E., Efremova, A. S., Melyanovskaya, Y. L., Voronkova, A. Y., Polyakov, A. V., Bulatenko, N., Adyan, T., Давидовна, Ш. В., Kovalskaia, V. A., Petrova, N. V., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810377 · Cited by 26 · see citing works
“With the AUC values lower than 1000, the therapeutic effect of the prescribed medication is known to be insignificant or absent [11].”
BackgroundFürstová, E., Doušová, T., Beránek, J., Libik, M., Fila, L., Modrák, M., Cinek, O., Maçek, M., & Dřevı́nek, P. (2021) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2021.07.006 · Cited by 23 · see citing works
Self-citationNew Therapies to Correct the Cystic Fibrosis Basic Defect
Bergeron, C., & Cantin, A. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126193 · Cited by 22 · see citing works
Livnat, G., Dagan, A., Heching, M., Shmueli, E., Prais, D., Yaacoby‐Bianu, K., Stein, N., Mei‐Zahav, M., Gur, M., Cohen‐Cymberknoh, M., et al. (2022) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2022.10.011 · Cited by 20 · see citing works
Bierlaagh, M. C., Ramalho, A. S., Silva, I. A. L., Vonk, A. M., van den Bor, R. M., van Mourik, P., Pott, J., Suen, S. W. F., Boj, S. F., Vries, R. G. J., et al. (2024) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2024.04.014 · Cited by 21 · see citing works
Self-citationBerg, P., Sørensen, M. V., Rousing, A. Q., Olesen, H. V., Jensen‐Fangel, S., Jeppesen, M., & Leipziger, J. (2022) · Annals of Internal Medicine · doi:10.7326/m22-1741 · Cited by 20 · see citing works
Validating organoid-derived human intestinal monolayers for personalized therapy in cystic fibrosis
Birimberg‐Schwartz, L., Ip, W., Bartlett, C., Avolio, J., Vonk, A. M., Gunawardena, T. N. A., Du, K., Esmaeili, M., Beekman, J. M., Rommens, J. M., et al. (2023) · Life Science Alliance · doi:10.26508/lsa.202201857 · Cited by 20 · see citing works
“…in 2D HIO correlates with clinical response to therapy Drug response data generated in HNE and 3D HIO showed good correlations between the in vitro response to CFTR modulator drugs and the clinical response (Pranke et al, 2017; Berkers et al, 2019; Ramalho et al, 2021; Aalbers et al, 2022).”
Self-citationGerardo‐Nava, J., Jansen, J., Günther, D., Klasen, L., Thiebes, A. L., Nießing, B., Bergerbit, C., Meyer, A. A., Linkhorst, J., Barth, M., et al. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202301030 · Cited by 18 · see citing works
Cystic fibrosis transmembrane conductance regulator modulators for cystic fibrosis: a new dawn?
Edmondson, C. L., Course, C. W., & Doull, I. J. M. (2021) · Archives of Disease in Childhood · doi:10.1136/archdischild-2020-320680 · Cited by 18 · see citing works
Molecular Dynamics and Theratyping in Airway and Gut Organoids Reveal R352Q-CFTR Conductance Defect
Wong, S. L., Awatade, N. T., Astore, M. A., Allan, K. M., Carnell, M. J., Šlapetová, I., Chen, P., Setiadi, J., Pandzic, E., Fawcett, L. K., et al. (2022) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2021-0337oc · Cited by 18 · see citing works
“Our reference hNECs and organoids both 255 showed similar patterns of response to modulators when compared to previous studies, although the 256 magnitude of response is lower [11, 13, 15, 18].”
BackgroundResultInfluentialMitropoulou, G., Brandenberg, N., Hoehnel, S., Ceroni, C., Balmpouzis, Z., Blanchon, S., Dorta, G. O., Sauty, A., & Koutsokera, A. (2022) · European Respiratory Journal · doi:10.1183/13993003.01341-2022 · Cited by 18 · see citing works
Challenging the paradigm: moving from umbrella labels to treatable traits in airway disease
Bush, A., & Pavord, I. D. (2021) · Breathe · doi:10.1183/20734735.0053-2021 · Cited by 16 · see citing works
“This can be done using cells harvested by nasal brushing [18], or more usually in Europe, with organoids [19].”
BackgroundOrganoid Technology and Its Role for Theratyping Applications in Cystic Fibrosis
Conti, J., Sorio, C., & Melotti, P. (2022) · Children · doi:10.3390/children10010004 · Cited by 16 · see citing works
“In addition, in vitro CFTR modulator responses in OG displayed excellent accuracy for stratifying drug responders from non-drug responders [68,74] suggesting the organoid model is suitable for guiding label extension or compassionate use for PwCF with rare genotypes [71,75].”
BackgroundOrganoids: A new frontier in precision medicine and engineering
Gao, Q., Wu, Y., Mao, Y., Chen, X., Geng, Z., & Su, J. (2025) · Precision medicine and engineering. · doi:10.1016/j.preme.2025.100049 · Cited by 17 · see citing works
Gunawardena, T. N. A., Bozóky, Z., Bartlett, C., Ouyang, H., Eckford, P. D. W., Moraes, T. J., Ratjen, F. A., Gonska, T. Y., & Bear, C. E. (2023) · Cells · doi:10.3390/cells12081174 · Cited by 15 · see citing works
“The aim of CFTR modulator theratyping using patient-derived tissue cultures is to support precision medicine for people harbouring rare, disease-causing mutations in CFTR [1,2].”
BackgroundAdvances in the pathogenesis and personalised treatment of paediatric asthma
Scotney, E., Fleming, L., Saglani, S., Sonnappa, S., & Bush, A. (2023) · BMJ Medicine · doi:10.1136/bmjmed-2022-000367 · Cited by 15 · see citing works
“114 115 Of course, a polygenic, environmentally modulated disease such as asthma is far more complex, but the example of cystic fibrosis should encourage researchers to discover more about basic biology and spread the benefits across the developmental course of the disease.”
BackgroundKumar, D., Gupta, S., Gupta, V., Tanwar, R., & Chandel, A. (2025) · Stem Cell Reviews and Reports · doi:10.1007/s12015-025-10893-w · Cited by 17 · see citing works
“…therapy with Ivacaftor and Lumacaftor, as reported by Dekkers et al. Additionally, observational studies by Berkers et al. [127] and Ramalho et al. [128] involving 24 and 97 patients, respectively, revealed a strong correlation between organoid responses and patient outcomes, with an AUROC of 0.94…”
InfluentialMuilwijk, D., Bierlaagh, M. C., van Mourik, P., Kraaijkamp, J., van der Meer, R., van den Bor, R. M., Heijerman, H. G. M., Eijkemans, M. J. C., Beekman, J. M., & van der Ent, C. K. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11121376 · Cited by 14 · see citing works
Self-citationWong, S. L., Awatade, N. T., Astore, M. A., Allan, K. M., Carnell, M. J., Šlapetová, I., Chen, P., Capraro, A., Fawcett, L. K., Whan, R. M., et al. (2021) · iScience · doi:10.1016/j.isci.2021.103710 · Cited by 13 · see citing works
“Mounting evidence has shown that in vitro functional studies in patient-derived cell models successfully predict clinical benefit of available CFTR modulators for individuals bearing ultra-rare mutations (Berkers et al., 2019; McCarthy et al., 2018; Ramalho et al., 2021).”
BackgroundPersonalized Selection of a CFTR Modulator for a Patient with a Complex Allele [L467F;F508del]
Kondratyeva, E., Bulatenko, N., Melyanovskaya, Y. L., Efremova, A. S., Zhekaite, E. K., Давидовна, Ш. В., Voronkova, A. Y., Карловна, А. И., Polyakov, A. V., Adyan, T., et al. (2022) · Current Issues in Molecular Biology · doi:10.3390/cimb44100349 · Cited by 13 · see citing works
“When the AUC value is lower than 1000, therapy with CFTR modulators cannot be recommended to patients since their appointment will not lead to a visible therapeutic effect [21].”
BackgroundBacalhau, M., Camargo, M., & Lopes‐Pacheco, M. (2024) · Journal of Personalized Medicine · doi:10.3390/jpm14010093 · Cited by 11 · see citing works
“Indeed, a high correlation between modulator-promoted responses in intestinal organoids and alterations in SCC and ppFEV1 in PwCF carrying common and rare variants has been reported in several studies [24,50,53].”
BackgroundComprehensive Assessment of CFTR Modulators’ Therapeutic Efficiency for N1303K Variant
Efremova, A. S., Kashirskaya, N. Y., Krasovskiy, S., Melyanovskaya, Y. L., Krasnova, M., Олеговна, М. Д., Bulatenko, N., Kondratyeva, E., Makhnach, O. V., Bukharova, T. B., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052770 · Cited by 11 · see citing works
“For AUC values below 1000 arbitrary units, targeted drug treatment is not recommended, as it will not provide a significant therapeutic effect [22].”
BackgroundThree-Dimensional Airway Spheroids and Organoids for Cystic Fibrosis Research
Laselva, O., & Conese, M. (2021) · Journal of Respiration · doi:10.3390/jor1040022 · Cited by 11 · see citing works
“Importantly, based on the organoid results, two subjects with rare mutations (Q359K_T360K and E60K) started modulator treatment, resulting in a major clinical benefit [61].”
BackgroundEfremova, A. S., Melyanovskaya, Y. L., Krasnova, M., Voronkova, A. Y., Олеговна, М. Д., Zhekaite, E. K., Bulatenko, N., Makhnach, O. V., Bukharova, T. B., Kutsev, S. I., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910424 · Cited by 10 · see citing works
Intestinal organoids: The path towards clinical application
Sugihara, H. Y., Okamoto, R., & Mizutani, T. (2024) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2024.151474 · Cited by 11 · see citing works
Bampi, G., Ramalho, A. S., Santos, L. A., Wagner, J., Dupont, L., Cuppens, H., Boeck, K. D., & Ignatova, Z. (2020) · Life · doi:10.3390/life11010014 · Cited by 10 · see citing works
“Crypts were isolated from rectal biopsies collected as described earlier [24].”
MethodSelf-citationHuman Induced Lung Organoids: A Promising Tool for Cystic Fibrosis Drug Screening
Demchenko, A. G., Balyasin, M. V., Nazarova, A. G., Grigorieva, O., Panchuk, I., Kondrateva, E. V., Tabakov, V. Y., Shchagina, O., Amelina, E., & Smirnikhina, S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26020437 · Cited by 9 · see citing works
“1+ lung progenitors. derived from Two time points (5 and 24 h) and a range of forskolin concentrations (1–20 µM) were selected on the basis of previous studies [12,18,20,26,27]. hiPSCs, it is 4.5–24 h [19,21,28].”
InfluentialMier, N. R., Cuyx, S., Boeck, K. D., Proesmans, M., Boon, M., Dupont, L., Arnauts, K., Wachter, E. D., Biervliet, S. V., Lequesne, M., et al. (2025) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2025.08.011 · Cited by 9 · see citing works
Self-citationCholon, D. M., & Gentzsch, M. (2022) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2022.102210 · Cited by 9 · see citing works
Competitive fitness of Pseudomonas aeruginosa isolates in human and murine precision-cut lung slices
Cramer, N., Nawrot, M. L., Wege, L., Dorda, M., Sommer, C., Danov, O., Wronski, S., Braun, A. C., Jonigk, D. D., Fischer, S., et al. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.992214 · Cited by 9 · see citing works
Theranostics vs theratyping or theranostics plus theratyping?
Amaral, M. D., & Pankonien, I. (2024) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2024.09.013 · Cited by 8 · see citing works
Conti, J., Angyal, D., Kleinfelder, K., Latorre, R. V., Calicchia, M., Farinazzo, A., Rodella, L., Tomba, F., Massella, A., Frulloni, L., et al. (2025) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2025.02.008 · Cited by 9 · see citing works
How to Choose the Correct Drug in Severe Pediatric Asthma
Bush, A. (2022) · Frontiers in Pediatrics · doi:10.3389/fped.2022.902168 · Cited by 9 · see citing works
“The other example is the use of in vitro testing of novel therapies using cells harvested by nasal brushing or the generation of rectal organoids has been shown to correlate with in vivo treatment response (93, 94).”
Bush, A. (2023) · Paediatric Respiratory Reviews · doi:10.1016/j.prrv.2023.11.001 · Cited by 8 · see citing works
Was ist gesichert in der Therapie der Mukoviszidose?
Ringshausen, F. C., Hellmuth, T., & Dittrich, A.-M. (2020) · Der Internist · doi:10.1007/s00108-020-00896-9 · Cited by 8 · see citing works
Krasnova, M., Melyanovskaya, Y. L., Krasovskiy, S., Bulatenko, N., Efremova, A. S., Bukharova, T. B., & Goldshtein, D. V. (2023) · PULMONOLOGIYA · doi:10.18093/0869-0189-2023-33-2-233-242 · Cited by 8 · see citing works
Intestinal organoid technology and applications in probiotics
Tan, H., Chen, X., Wang, C., Song, J., Xu, J., Zhang, Y., & Suo, H. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2023.2288887 · Cited by 8 · see citing works
“For example, CF patient-derived intestinal organoids were used to assess the functional recovery of the CF transmembrane conductance regulator (CFTR) (Boj et al. 2017) and to guide personalized medicine strategies for CF patients by measuring CFTR function (Ramalho et al. 2021) (Table 1).”
Biomedical applications of organoids in genetic diseases
Huang, W., Jeong, S., Kim, W., & Chen, L. (2024) · Medical Review · doi:10.1515/mr-2024-0077 · Cited by 7 · see citing works
Epithelial and mesenchymal fate decisions in Wolffian duct development
Crossen, M. J., Wilbourne, J., Fogarty, A., & Zhao, F. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.05.007 · Cited by 7 · see citing works
Mei‐Zahav, M., Orenti, A., Jung, A., & Kerem, E. (2024) · ERJ Open Research · doi:10.1183/23120541.00587-2024 · Cited by 7 · see citing works
“[13], in their examination of residual CFTR function in different RF variants using Forskolin-induced organoid swelling, found varying responses among these variants, which correlated with sweat chloride levels.”
Cinek, O., Fürstová, E., Novotna, S., Hubáčková, K., Doušová, T., Bořek-Dohalská, L., & Dřevı́nek, P. (2024) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2024.09.005 · Cited by 7 · see citing works
Self-citationPrecision medicine in cystic fibrosis: predictive role of forskolin-induced swelling assay
Fürstová, E., Dřevı́nek, P., Novotna, S., Libik, M., Benešová, K., Bořek-Dohalská, L., Sakmarova, K., Modrák, M., Maçek, M., & Doušová, T. (2024) · European Respiratory Journal · doi:10.1183/13993003.00156-2024 · Cited by 6 · see citing works
Self-citationCFTR modulators response of S737F and T465N CFTR variants on patient-derived rectal organoids
Kleinfelder, K., Melotti, P., Hristodor, A. M., Fevola, C., Taccetti, G., Terlizzi, V., & Sorio, C. (2024) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-024-03334-3 · Cited by 7 · see citing works
Organoid-on-a-chip (OrgOC): Advancing cystic fibrosis research
Zheng, M., Erice, E., Wang, H., Zhang, L., & Lawrie, C. H. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2025.102148 · Cited by 8 · see citing works
Recent developments in cystic fibrosis drug discovery: where are we today?
Lopes‐Pacheco, M., Winters, A. G., Jackson, J. J., Olson, J. A., Kim, M., Ledwitch, K. V., Tedman, A., Jhangiani, A. R., Schlebach, J. P., Meiler, J., et al. (2025) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2025.2490250 · Cited by 5 · see citing works
“Indeed, results from intestinal organoids have demonstrated good correlations with modulator-induced changes in PwCF, namely sweat chloride concentration and lung function [100,104,105].”
Kondratyeva, E., Melyanovskaya, Y. L., Bulatenko, N., Davydenko, K., Filatova, A. Y., Efremova, A. S., Skoblov, M. Y., Bukharova, T. B., Давидовна, Ш. В., Voronkova, A. Y., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076351 · Cited by 6 · see citing works
“The results obtained on intestinal organoids correlate with the data provided by Ramalho and co-authors in the article 2021 [30] for a patient with genotype E92K/18111.”
ResultAluma, B. E. B., Reiter, J. M., Efrati, O., Bezalel, Y., Keler, S., Ashkenazi, M., Dagan, A., Buchnik, Y., Sadras, I., & Cohen‐Cymberknoh, M. (2024) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2024.02.008 · Cited by 6 · see citing works
An update on targeting airway inflammation in cystic fibrosis
Mullen, E., Murphy, M. P., Bateman, G., Casey, M., Gunaratnam, C., & McElvaney, N. G. (2025) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2025.2517898 · Cited by 5 · see citing works
Railean, V., Rodrigues, C. S., Pankonien, I., Ramalho, S. S., Silva, I. A. L., Doušová, T., Castanhinha, S., Azevedo, P., Roda, J., Farinha, C. M., et al. (2025) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-025-00806-5 · Cited by 5 · see citing works
“Although our study is limited by the small cohort size, a larger cohort would provide a broader basis to confirm correlations as shown in previous studies, reinforcing the relevance of this assay for predicting pwCF-specific responses to CFTRm [26, 27].”
Amelina, E., Efremova, A. S., Melyanovskaya, Y. L., Bulatenko, N., Bukharova, T. B., Kashirskaya, N. Y., Krasovskiy, S., & Goldshtein, D. V. (2021) · PULMONOLOGIYA · doi:10.18093/0869-0189-2021-31-2-167-177 · Cited by 5 · see citing works
Role of Biliary Organoids in Cholestasis Research and Regenerative Medicine
Soroka, C. J., Roberts, S. J., Boyer, J. L., & Assis, D. N. (2021) · Seminars in Liver Disease · doi:10.1055/s-0041-1728663 · Cited by 5 · see citing works
Novel Applications of Biomarkers and Personalized Medicine in Cystic Fibrosis
Guimbellot, J. S., Nichols, D. P., & Brewington, J. J. (2022) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2022.06.005 · Cited by 5 · see citing works
Zhang, Y., Yang, N., Li, Q., Tang, Y., Bai, B., & Liu, G. (2025) · Virology · doi:10.1016/j.virol.2025.110595 · Cited by 4 · see citing works
Pauw, E. D., Gommers, B., Ensinck, M. M., Timmerman, S., Vriendt, S. D., Bueds, C., Wei, M., Hermans, F., Arnauts, K., Ramalho, A. S., et al. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05627-7 · Cited by 3 · see citing works
Self-citationCuyx, S., Ramalho, S. S., Callebaut, I., Cuppens, H., Kmit, A. H. P., Arnauts, K., Ferrante, M., Verfaillie, C. M., Ensinck, M. M., Carlon, M. S., et al. (2022) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2022.05.013 · Cited by 4 · see citing works
Self-citationCharting the path to expanded access for CFTR modulator drugs: the nose knows
Bear, C. E., & Ratjen, F. A. (2023) · European Respiratory Journal · doi:10.1183/13993003.01387-2023 · Cited by 4 · see citing works
Functional activity of the CFTR channel in a patient with the [L467F;F508del]/W1310X genotype
Krasnova, M., Олеговна, М. Д., Efremova, A. S., Melyanovskaya, Y. L., Sherman, V. D., Bukharova, T. B., & Goldshtein, D. V. (2024) · PULMONOLOGIYA · doi:10.18093/0869-0189-2024-34-2-264-270 · Cited by 4 · see citing works
Yan, R., Zhang, Z., de Jonge, H. R., Lin, R., Yu, H., Sarker, R., Boffelli, D., Zwick, R. K., Klein, O. D., Tse, C., et al. (2025) · iScience · doi:10.1016/j.isci.2025.112453 · Cited by 3 · see citing works
“21–23 Since CFTR was expressed in PD enteroids, we compared the FIS response in UD, PD, and FD (fully differentiated) NHS (normal healthy subject) and F508del-CF colonic/ rectal enteroids.”
Boeck, K. D., Burgel, P., Bierlaagh, M. C., Hill, K., Amaral, M. D., Birimberg‐Schwartz, L., Brewington, J. J., Davies, J. C., Karadag, B. T., Martin, U., et al. (2026) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2026.04.013 · Cited by 4 · see citing works
Self-citationThe effectiveness of CFTR modulators in people with CF and rare mutations: A real‐world study
Hanger, S., Felton, I. C., Ukor, E.-F., Bowman, E., Caldwell, C., BANYA, W. A. S., Madge, S. L., Jones, A., & Simmonds, N. J. (2023) · Pediatric Pulmonology · doi:10.1002/ppul.26713 · Cited by 2 · see citing works
An innovative strategy for personalised medicine in a CFSPID case that evolved with time
Twynam-Perkins, J., Fall, A., Lefferts, J. W., & Urquhart, D. S. (2023) · Paediatric Respiratory Reviews · doi:10.1016/j.prrv.2023.06.001 · Cited by 3 · see citing works
Advances in the Study of Common and Rare CFTR Complex Alleles Using Intestinal Organoids
Krasnova, M., Efremova, A. S., Олеговна, М. Д., Bukharova, T. B., Kashirskaya, N. Y., Kutsev, S. I., Kondratyeva, E., & Goldshtein, D. V. (2024) · Journal of Personalized Medicine · doi:10.3390/jpm14020129 · Cited by 2 · see citing works
Organoids in Genetic Disorders: from Disease Modeling to Translational Applications
Zhu, Y., Lin, N., Li, J., Zhang, H., Zhang, P., Cheng, X., Yang, Q., & Liu, L. (2025) · Stem Cell Reviews and Reports · doi:10.1007/s12015-025-10973-x · Cited by 2 · see citing works
“Rectal biopsy-derived organoids from CF patients enabled functional assessment of CFTR activity and modulator efficacy, correlating strongly with clinical outcomes [95].”
Research Advances and Disease Modeling in Respiratory Organoids
Chu, L., Chen, D., Jiang, S., Long, H., Liu, X., & Chen, Y. (2026) · Biomedicines · doi:10.3390/biomedicines14010221 · Cited by 2 · see citing works
“These organoids showed CFTR -dependent swelling upon forskolin stimulation (a forskolin-induced swelling test widely used to assess CFTR -dependent fluid secretion and predict drug responses in CF patients) [129,130].”
Treatment effects of CFTR modulators on people with cystic fibrosis carrying the Q359K/T360K variant
Yaacoby‐Bianu, K., Heching, M., Kramer, M. R., Shmueli, E., Prais, D., Vermeulen, F. L., Ramalho, A. S., Cohen, R., Livnat, G., & Shteinberg, M. (2024) · ERJ Open Research · doi:10.1183/23120541.00386-2024 · Cited by 2 · see citing works
“The treatment of the patient with LI also resulted in a significant clinical response [5].”
Self-citationCystic fibrosis and other ion channel-related diseases
Graeber, S. Y., & Mall, M. A. (2023) · European Respiratory Society eBooks · doi:10.1183/2312508x.10018022 · Cited by 2 · see citing works
Kondratyeva, E., Voronkova, A. Y., Efremova, A. S., Melyanovskaya, Y. L., Bulatenko, N., Bukharova, T. B., Odinaeva, N. D., de Jonge, H. R., & Goldstein, D. V. (2022) · Voprosy praktičeskoj pediatrii · doi:10.20953/1817-7646-2022-3-74-82 · Cited by 2 · see citing works
EMC3 is critical for CFTR function and calcium mobilization in the mouse intestinal epithelium
Penrod, S., Tang, X., Moon, C., Whitsett, J. A., Naren, A. P., & Huang, Y. (2024) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00066.2024 · Cited by 1 · see citing works
N1303K (p.Asn1303Lys) variant: Expanding frontiers in the treatment of cystic fibrosis
Pacheco, J., Almeida, L. M., Boaventura, R. D. P., Pereira, A. L., Rodrigues, C. S., Railean, V., Silva, I. A. L., Pankonien, I., Amaral, M. D., & Amorim, A. A. (2025) · Respiratory Medicine · doi:10.1016/j.rmed.2025.108238 · Cited by 1 · see citing works
Graeber, S. Y., & Frost, F. J. (2025) · ERJ Open Research · doi:10.1183/23120541.00593-2025 · Cited by 1 · see citing works
Latorre, R. V., Mortali, C., Lotti, V., Kleinfelder, K., Melotti, P., & Sorio, C. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.178612 · Cited by 2 · see citing works
Towards functional precision medicine? Evidence standards of organoids as patient-specific models
Green, S., Vogt, H., & Gaillard, M. (2026) · History & Philosophy of the Life Sciences · doi:10.1007/s40656-026-00720-x · Cited by 1 · see citing works
“(senior researcher, industry) Before then, and parallel to the early implementation, observational trials had documented the correlation between the response of PDOs in vitro to drug cocktails and clinical indicators (Dekkers et al., 2016 , Berkers et al., 2019 , Ramalho et al., 2021).”
Muilwijk, D., de Poel, E., van Mourik, P., Suen, S. W. F., Vonk, A. M., Brunsveld, J. E., Kruisselbrink, E., Oppelaar, H., Hagemeijer, M. C., Berkers, G., et al. (2021) · medRxiv · doi:10.1101/2021.02.01.21250609
Self-citationMaking Research Flourish Through ESPGHAN
Gasparetto, M., Strisciuglio, C., Assa, A., Gerasimidis, K., Giachero, F., Nowak, J. K., Robinson, P. S., Tél, B., Zilbauer, M., & Jenke, A. C. W. (2021) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000003250
- Authors
- Ramalho, A. S., Fürstová, E., Vonk, A. M., Ferrante, M., Verfaillie, C., Dupont, L., Boon, M., Proesmans, M., Beekman, J. M., Sarouk, I., Vazquez Cordero, C., Vermeulen, F., & De Boeck, K.
- Affiliations
- KU Leuven (BE)
- Charles University (CZ)
- University Medical Center Utrecht (NL)
- Universitair Ziekenhuis Leuven (BE)
- Sheba Medical Center (IL)
- ORCID
- Venue
- European Respiratory Journal
- Publisher
- European Respiratory Society (ERS)
- Published
- 2020-08-03
- Volume
- 57
- Issue
- 1
- Pages
- 1902426
- ISSN
- 0903-1936 (ISSN-L)
- 1399-3003
- OpenAlex
- W3047301928
- Cited by
- 121
- References
- 32
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 17 · 2023: 23 · 2022: 25 · 2021: 22 · 2020: 4
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Respiratory Journal (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion, other-oa)
- Funders
- Fonds Wetenschappelijk Onderzoek (C3 project)
- Belgian CF patients’ association “Mucoverening”
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- cystic fibrosis, CFTR mutations, intestinal organoids, CFTR function, CFTR modulators, CFTR correctors, CFTR potentiators, sweat chloride, lung function, precision medicine, rare CFTR mutations, in vitro disease model
- MeSH terms
- Cystic Fibrosis, Homozygote, Humans, Mutation, Organoids, Ion Transport, Cystic Fibrosis Transmembrane Conductance Regulator
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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