{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:56:30Z","timestamp":1780404990217,"version":"3.54.1"},"reference-count":156,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cystic fibrosis (CF) is caused by loss-of-function variants in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride and bicarbonate channel and affects multiple organs, with pancreatic involvement showing very high penetrance. In pancreatic ducts, CFTR drives secretion of alkaline, bicarbonate-rich fluid that maintains intraductal patency, neutralises gastric acid and permits safe delivery of digestive enzymes. Selective impairment of CFTR-dependent bicarbonate transport, even in the presence of residual chloride conductance, is strongly associated with exocrine pancreatic insufficiency, recurrent pancreatitis and cystic-fibrosis-related diabetes. These clinical manifestations are captured by pharmacodynamic anchors such as faecal elastase-1, steatorrhoea, pancreatitis burden and glycaemic control, providing clinically meaningful benchmarks for CFTR-targeted therapies. In this review, we summarise the principal mechanisms underlying pancreatic pathophysiology and the current approaches to clinical management. We then examine in vitro pancreatic duct models that are used to evaluate small molecules and emerging therapeutics targeting CFTR. These experimental systems include native tissue, primary cultures, organoids, co-cultures and microfluidic devices, each of which has its own advantages and limitations. Intact micro-perfused ducts provide the physiological benchmark for studying luminal pH control and bicarbonate (HCO3\u2212) secretion. Primary pancreatic duct epithelial cells (PDECs) and pancreatic ductal organoids (PDO) preserve ductal identity, patient-specific genotype and key regulatory networks. Immortalised ductal cell lines grown on permeable supports enable scalable screening and structure activity analyses. Co-culture models and organ-on-chip devices incorporate inflammatory, stromal and endocrine components together with flow and shear and provide system-level readouts, including duct-islet communication. Across this complementary toolkit, we prioritise bicarbonate-relevant endpoints, including luminal and intracellular pH and direct measures of HCO3\u2212 flux, to improve alignment between in vitro pharmacology and clinical pancreatic outcomes. The systematic use of complementary models should facilitate the discovery of next-generation CFTR modulators and adjunctive strategies with the greatest potential to protect both exocrine and endocrine pancreatic function in people with CF.<\/jats:p>","DOI":"10.3390\/ijms27031279","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T15:41:56Z","timestamp":1769528516000},"page":"1279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cystic Fibrosis of the Pancreas: In Vitro Duct Models for CFTR-Targeted Translational Research"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9797-5754","authenticated-orcid":false,"given":"Alessandra","family":"Ludovico","sequence":"first","affiliation":[{"name":"Istituto di Biofisica, Consiglio Nazionale delle Ricerche (CNR), Via De Marini 6, 16149 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Battistini","sequence":"additional","affiliation":[{"name":"Istituto di Biofisica, Consiglio Nazionale delle Ricerche (CNR), Via De Marini 6, 16149 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8764-2468","authenticated-orcid":false,"given":"Debora","family":"Baroni","sequence":"additional","affiliation":[{"name":"Istituto di Biofisica, Consiglio Nazionale delle Ricerche (CNR), Via De Marini 6, 16149 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/humu.10041","article-title":"Cystic fibrosis: A worldwide analysis of CFTR mutations, correlation with incidence data and application to screening","volume":"19","author":"Bobadilla","year":"2002","journal-title":"Hum. Mutat."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.jcf.2008.03.007","article-title":"The prevalence of cystic fibrosis in the European Union","volume":"7","author":"Farrell","year":"2008","journal-title":"J. Cyst. Fibros."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S2213-2600(16)00053-9","article-title":"Newborn screening for cystic fibrosis","volume":"4","author":"Castellani","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"15010","DOI":"10.1038\/nrdp.2015.10","article-title":"Cystic fibrosis","volume":"1","author":"Ratjen","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1126\/science.2475911","article-title":"Identification of the cystic fibrosis gene, cloning and characterization of complementary DNA","volume":"245","author":"Riordan","year":"1989","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1152\/physrev.1999.79.1.S23","article-title":"Structure and function of the CFTR chloride channel","volume":"79","author":"Sheppard","year":"1999","journal-title":"Physiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00018-016-2391-y","article-title":"Role of CFTR in epithelial physiology","volume":"74","author":"Gray","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1085\/jgp.200810122","article-title":"CFTR functions as a bicarbonate channel in pancreatic duct cells","volume":"133","author":"Ishiguro","year":"2009","journal-title":"J. Gen. Physiol."},{"key":"ref_10","unstructured":"(2025, December 01). Cystic Fibrosis Mutation Database. Hospital for Sick Children. Available online: http:\/\/www.genet.sickkids.on.ca."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1016\/S2213-2600(16)30189-8","article-title":"Classification of CFTR mutation classes, authors\u2019 reply","volume":"4","author":"Amaral","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.jcf.2013.12.003","article-title":"The relative frequency of CFTR mutation classes in European patients with cystic fibrosis","volume":"13","author":"Zolin","year":"2014","journal-title":"J. Cyst. Fibros."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.biocel.2014.02.023","article-title":"Genetics of cystic fibrosis, CFTR mutation classifications toward genotype-based CF therapies","volume":"52","author":"Fanen","year":"2014","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"210112","DOI":"10.1183\/20734735.0112-2021","article-title":"Progress in precision medicine in cystic fibrosis, a focus on CFTR modulator therapy","volume":"17","author":"Tewkesbury","year":"2021","journal-title":"Breathe"},{"key":"ref_15","first-page":"279","article-title":"Cystic fibrosis therapy, from symptoms to the cause of the disease","volume":"29","author":"Kireeva","year":"2025","journal-title":"Vavilovskii Zhurnal Genet. Selektsii."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lopes-Pacheco, M. (2020). CFTR modulators, the changing face of cystic fibrosis in the era of precision medicine. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01662"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/nsmb882","article-title":"The \u0394F508 cystic fibrosis mutation impairs domain-domain interactions and arrests post-translational folding of CFTR","volume":"12","author":"Du","year":"2005","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"102214","DOI":"10.1016\/j.coph.2022.102214","article-title":"Overview of CF lung pathophysiology","volume":"64","author":"Cabrini","year":"2022","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mad\u00e1csy, T., Pallagi, P., and Mal\u00e9th, J. (2018). Cystic fibrosis of the pancreas, the role of CFTR channel in intracellular Ca2+ signaling and mitochondrial function in the exocrine pancreas. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.01585"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/path.4634","article-title":"Pancreatic pathophysiology in cystic fibrosis","volume":"238","author":"Meyerholz","year":"2016","journal-title":"J. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1002\/ppul.26958","article-title":"Pancreatitis in cystic fibrosis, presentation, medical and surgical management, and the impact of modulator therapies","volume":"59","author":"Milano","year":"2024","journal-title":"Pediatr. Pulmonol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Malik, S.S., Padmanabhan, D., and Hull-Meichle, R.L. (2023). Pancreas and islet morphology in cystic fibrosis, clues to the etiology of cystic fibrosis-related diabetes. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1269139"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/S0022-3476(05)80032-0","article-title":"Pancreatic endocrine function in cystic fibrosis","volume":"118","author":"Moran","year":"1991","journal-title":"J. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1164\/rccm.201403-0576OC","article-title":"Diabetes-related mortality in adults with cystic fibrosis, role of genotype and sex","volume":"191","author":"Lewis","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/0016-5085(88)90490-8","article-title":"Impaired chloride secretion, as well as bicarbonate secretion, underlies the fluid secretory defect in the cystic fibrosis pancreas","volume":"95","author":"Kopelman","year":"1988","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1056\/NEJM198502073120601","article-title":"Pancreatic fluid secretion and protein hyperconcentration in cystic fibrosis","volume":"312","author":"Kopelman","year":"1985","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Angyal, D., Bijvelds, M.J.C., Bruno, M.J., Peppelenbosch, M.P., and de Jonge, H.R. (2021). Bicarbonate transport in cystic fibrosis and pancreatitis. Cells, 11.","DOI":"10.3390\/cells11010054"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.jcf.2022.08.008","article-title":"CFTR modulators and the exocrine pancreas, a scoping review","volume":"22","author":"Ramsey","year":"2023","journal-title":"J. Cyst. Fibros."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e68","DOI":"10.1038\/ctg.2014.13","article-title":"The common CTRC variant G60G increases risk of chronic pancreatitis but not recurrent acute pancreatitis","volume":"6","author":"LaRusch","year":"2015","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1136\/gutjnl-2011-300645","article-title":"CFTR, SPINK1, CTRC and PRSS1 variants in chronic pancreatitis, is the role of mutated CFTR overestimated?","volume":"62","author":"Rosendahl","year":"2013","journal-title":"Gut"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1001\/archpedi.1938.01980140114013","article-title":"Cystic fibrosis of the pancreas and its relation to celiac disease, a clinical and pathologic study","volume":"56","author":"Andersen","year":"1938","journal-title":"Am. J. Dis. Child."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"336","DOI":"10.2152\/jmi.56.336","article-title":"The role of CFTR in bicarbonate secretion by pancreatic duct and airway epithelia","volume":"56","author":"Kim","year":"2009","journal-title":"J. Med. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1053\/j.gastro.2010.04.004","article-title":"Dynamic regulation of CFTR bicarbonate permeability by intracellular chloride and its role in pancreatic bicarbonate secretion","volume":"139","author":"Park","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1053\/j.gastro.2010.07.051","article-title":"Protons released during pancreatic acinar cell secretion acidify the lumen and contribute to pancreatitis in mice","volume":"139","author":"Behrendorff","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1097\/MPA.0000000000000421","article-title":"The physiology and pathophysiology of pancreatic ductal secretion, the background for clinicians","volume":"44","author":"Pallagi","year":"2015","journal-title":"Pancreas"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bal\u00e1zs, A., Balla, Z., Kui, B., Mal\u00e9th, J., Rakonczay, Z., Duerr, J., Zhou-Suckow, Z., Schatterny, J., Sendler, M., and Mayerle, J. (2018). Ductal mucus obstruction and reduced fluid secretion are early defects in chronic pancreatitis. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00632"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"a009746","DOI":"10.1101\/cshperspect.a009746","article-title":"The cystic fibrosis of the exocrine pancreas","volume":"3","author":"Wilschanski","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_38","first-page":"97","article-title":"Pathophysiology of the pancreas in cystic fibrosis","volume":"41","author":"Durie","year":"1992","journal-title":"Neth. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrgastro.2015.226","article-title":"Cystic fibrosis from the gastroenterologist\u2019s perspective","volume":"13","author":"Ooi","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1056\/NEJM199809033391002","article-title":"Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis","volume":"339","author":"Cohn","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1097\/MOG.0b013e328349e2f8","article-title":"Genetics of pancreatitis","volume":"27","author":"LaRusch","year":"2011","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/112_2015_5002","article-title":"CFTR, a new horizon in the pathomechanism and treatment of pancreatitis","volume":"170","author":"Hegyi","year":"2016","journal-title":"Rev. Physiol. Biochem. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1002\/humu.21511","article-title":"Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens","volume":"32","author":"Steiner","year":"2011","journal-title":"Hum. Mutat."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.2337\/dc09-0586","article-title":"Cystic fibrosis\u2013related diabetes, current trends in prevalence, incidence, and mortality","volume":"32","author":"Moran","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17231","DOI":"10.1038\/s41598-017-17404-z","article-title":"Structural abnormalities in islets from very young children with cystic fibrosis may contribute to cystic fibrosis-related diabetes","volume":"7","author":"Bogdani","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e98240","DOI":"10.1172\/jci.insight.98240","article-title":"Cystic fibrosis\u2013related diabetes is caused by islet loss and inflammation","volume":"3","author":"Hart","year":"2018","journal-title":"JCI Insight"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.jcf.2013.02.008","article-title":"Update on cystic fibrosis-related diabetes","volume":"12","author":"Kelly","year":"2013","journal-title":"J. Cyst. Fibros."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"200293","DOI":"10.1183\/16000617.0293-2020","article-title":"Cystic fibrosis-related diabetes and lung disease, an update","volume":"30","author":"Prentice","year":"2021","journal-title":"Eur. Respir. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0022-3476(82)80501-5","article-title":"Improved respiratory prognosis in patients with cystic fibrosis with normal fat absorption","volume":"100","author":"Gaskin","year":"1982","journal-title":"J. Pediatr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.jpeds.2015.07.044","article-title":"Early life growth trajectories in cystic fibrosis are associated with pulmonary function at age 6 years","volume":"167","author":"Sanders","year":"2015","journal-title":"J. Pediatr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.clnu.2023.12.017","article-title":"ESPEN-ESPGHAN-ECFS guideline on nutrition care for cystic fibrosis","volume":"43","author":"Wilschanski","year":"2024","journal-title":"Clin. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.jpeds.2004.04.049","article-title":"Use of fecal elastase-1 to classify pancreatic status in patients with cystic fibrosis","volume":"145","author":"Borowitz","year":"2004","journal-title":"J. Pediatr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.jcf.2015.12.024","article-title":"Measurement of fecal elastase improves performance of newborn screening for cystic fibrosis","volume":"15","author":"Barben","year":"2016","journal-title":"J. Cyst. Fibros."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5128760","DOI":"10.1155\/2017\/5128760","article-title":"Imaging the abdominal manifestations of cystic fibrosis","volume":"2017","author":"Gillespie","year":"2017","journal-title":"Int. J. Hepatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1203\/00006450-198603000-00002","article-title":"Age-related alterations of immunoreactive pancreatic cationic trypsinogen in sera from cystic fibrosis patients with and without pancreatic insufficiency","volume":"20","author":"Durie","year":"1986","journal-title":"Pediatr. Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Freswick, P.N., Reid, E.K., and Mascarenhas, M.R. (2022). Pancreatic enzyme replacement therapy in cystic fibrosis. Nutrients, 14.","DOI":"10.3390\/nu14071341"},{"key":"ref_57","first-page":"CD013488","article-title":"Timing of pancreatic enzyme replacement therapy in cystic fibrosis","volume":"8","author":"Ng","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Mariotti Zani, E., Grandinetti, R., Cunico, D., Torelli, L., Fainardi, V., Pisi, G., and Esposito, S. (2023). Nutritional care in children with cystic fibrosis. Nutrients, 15.","DOI":"10.3390\/nu15030479"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1053\/j.gastro.2010.09.046","article-title":"Type of CFTR mutation determines risk of pancreatitis in patients with cystic fibrosis","volume":"140","author":"Ooi","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1053\/gast.2002.37042","article-title":"Genotype and phenotype correlations in patients with cystic fibrosis and pancreatitis","volume":"123","author":"Durno","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1080\/17474124.2022.2084072","article-title":"Current clinical opinion on CFTR dysfunction and patient risk of pancreatitis: Diagnostic and therapeutic considerations","volume":"16","author":"Phadke","year":"2022","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1097\/MPG.0000000000001788","article-title":"Reduction of recurrence risk of pancreatitis in cystic fibrosis with ivacaftor: Case series","volume":"66","author":"Carrion","year":"2018","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.jcf.2023.02.013","article-title":"Acute pancreatitis in pancreatic-insufficient cystic fibrosis patients treated with CFTR modulators","volume":"22","author":"Sadras","year":"2023","journal-title":"J. Cyst. Fibros."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jcf.2021.11.012","article-title":"Effect of elexacaftor\u2013tezacaftor\u2013ivacaftor on body weight and metabolic parameters in adults with cystic fibrosis","volume":"21","author":"Petersen","year":"2022","journal-title":"J. Cyst. Fibros."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Petrocheilou, A., Kaditis, A.G., and Loukou, I. (2020). Pancreatitis in a patient with cystic fibrosis taking ivacaftor. Children, 7.","DOI":"10.3390\/children7010006"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e096","DOI":"10.1097\/PG9.0000000000000096","article-title":"Acute pancreatitis in a previously exocrine pancreatic-insufficient cystic fibrosis patient with improved pancreatic function after lumacaftor\/ivacaftor therapy","volume":"2","author":"Redman","year":"2021","journal-title":"JPGN Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.jcf.2019.03.009","article-title":"An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2\u20135 years (KLIMB)","volume":"18","author":"Rosenfeld","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.2337\/dc10-1768","article-title":"Clinical care guidelines for cystic fibrosis-related diabetes: A position statement of the American Diabetes Association and a clinical practice guideline of the Cystic Fibrosis Foundation","volume":"33","author":"Moran","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1111\/pedi.13453","article-title":"ISPAD Clinical Practice Consensus Guidelines 2022: Management of cystic fibrosis-related diabetes in children and adolescents","volume":"23","author":"Ode","year":"2022","journal-title":"Pediatr. Diabetes"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S2213-2600(18)30202-9","article-title":"Ivacaftor treatment of cystic fibrosis in children aged 12 to <24 months with a CFTR gating mutation (ARRIVAL): A phase 3 single-arm study","volume":"6","author":"Rosenfeld","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e01935-23","DOI":"10.1128\/mbio.01935-23","article-title":"Longitudinal profiling of the intestinal microbiome in children with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor","volume":"15","author":"Reasoner","year":"2024","journal-title":"mBio"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.jcf.2023.09.005","article-title":"Changes in fecal elastase-1 following initiation of CFTR modulator therapy in pediatric patients with cystic fibrosis","volume":"22","author":"Stephenson","year":"2023","journal-title":"J. Cyst. Fibros."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Coughlin, M.P., Sankararaman, S., Roesch, E.A., Certo, E.D., Brej, B.L., and Konstan, M.W. (2024). Case report: A delicate equilibrium of exocrine pancreatic recovery and hepatotoxicity with elexacaftor\/tezacaftor\/ivacaftor therapy in a pediatric patient with cystic fibrosis. Front. Pediatr., 12.","DOI":"10.3389\/fped.2024.1457517"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1513\/AnnalsATS.201909-671CME","article-title":"The extrapulmonary effects of cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis","volume":"17","author":"Sergeev","year":"2020","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.jcf.2021.09.010","article-title":"CFTR modulators increase risk of acute pancreatitis in pancreatic-insufficient patients with cystic fibrosis","volume":"21","author":"Gould","year":"2022","journal-title":"J. Cyst. Fibros."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"McKay, I.R., and Ooi, C.Y. (2022). The exocrine pancreas in cystic fibrosis in the era of CFTR modulation: A mini review. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.914790"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1038\/s41395-018-0123-7","article-title":"Ivacaftor CFTR potentiator therapy is efficient for pancreatic manifestations in cystic fibrosis","volume":"113","author":"Kounis","year":"2018","journal-title":"Am. J. Gastroenterol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Giordano, P., Leonetti, G., Granberg, V., Casolino, R.M.P., Lassandro, G., Delvecchio, M., and Linguiti, G. (2025). Effect of CFTR modulators on glucose homeostasis in children and young adults with cystic fibrosis-related diabetes: A systematic review. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1623654"},{"key":"ref_79","first-page":"100286","article-title":"The role of modulators in cystic fibrosis-related diabetes","volume":"27","author":"Merjaneh","year":"2021","journal-title":"J. Clin. Transl. Endocrinol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1097\/00006676-199303000-00017","article-title":"Isolation, culture, and characterization of human pancreatic duct cells","volume":"8","author":"Trautmann","year":"1993","journal-title":"Pancreas"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1083\/jcb.85.1.122","article-title":"Characterization of ducts isolated from the pancreas of the rat","volume":"85","author":"Githens","year":"1980","journal-title":"J. Cell Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/BF02633964","article-title":"Isolation and culture of intralobular ducts from the hamster pancreas","volume":"31","author":"Yuan","year":"1995","journal-title":"In Vitr. Cell. Dev. Biol. Anim."},{"key":"ref_83","first-page":"113","article-title":"Culture and immortalization of pancreatic ductal epithelial cells","volume":"103","author":"Lawson","year":"2005","journal-title":"Methods Mol. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"G1328","DOI":"10.1152\/ajpgi.1997.272.6.G1328","article-title":"Isolation and culture of bovine pancreatic duct epithelial cells","volume":"272","author":"Cotton","year":"1997","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1007\/BF02629092","article-title":"Isolation and monolayer culture of guinea pig pancreatic duct epithelial cells","volume":"24","author":"Hootman","year":"1988","journal-title":"In Vitr. Cell Dev. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11626-998-0126-6","article-title":"Culture of human main pancreatic duct epithelial cells","volume":"34","author":"Oda","year":"1998","journal-title":"In Vitr. Cell Dev. Biol. Anim."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1002\/1097-0142(19810315)47:6+<1505::AID-CNCR2820471411>3.0.CO;2-J","article-title":"Morphologic and biochemical characteristics of isolated and cultured pancreatic ducts","volume":"47","author":"Githens","year":"1981","journal-title":"Cancer"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Jones, C.J. (1990). Pancreatic ducts: Isolation, culture and bicarbonate transport. Epithelia, Springer.","DOI":"10.1007\/978-94-011-3905-2"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1113\/jphysiol.1991.sp018523","article-title":"Characteristics of fluid secretion from isolated rat pancreatic ducts stimulated with secretin and bombesin","volume":"435","author":"Ashton","year":"1991","journal-title":"J. Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1172\/JCI115358","article-title":"Localization of the cystic fibrosis transmembrane conductance regulator in pancreas","volume":"88","author":"Marino","year":"1991","journal-title":"J. Clin. Investig."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1148\/radiology.203.2.9114101","article-title":"Pancreatic duct: Morphologic and functional evaluation with dynamic MR pancreatography after secretin stimulation","volume":"203","author":"Matos","year":"1997","journal-title":"Radiology"},{"key":"ref_92","unstructured":"Ishiguro, H., Steward, M., and Yamamoto, A. (2011). Microperfusion and micropuncture analysis of ductal secretion. Medicine."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1038\/labinvest.2013.113","article-title":"Specific transduction and labeling of pancreatic ducts by targeted recombinant viral infusion into mouse pancreatic ducts","volume":"93","author":"Guo","year":"2013","journal-title":"Lab. Investig."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"a009571","DOI":"10.1101\/cshperspect.a009571","article-title":"Transepithelial bicarbonate secretion: Lessons from the pancreas","volume":"2","author":"Park","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1085\/jgp.20028631","article-title":"Membrane potential and bicarbonate secretion in isolated interlobular ducts from guinea-pig pancreas","volume":"120","author":"Ishiguro","year":"2002","journal-title":"J. Gen. Physiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1113\/jphysiol.2001.012490","article-title":"Chloride transport in microperfused interlobular ducts isolated from guinea-pig pancreas","volume":"539","author":"Ishiguro","year":"2002","journal-title":"J. Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"G1307","DOI":"10.1152\/ajpgi.90697.2008","article-title":"Functional coupling of apical Cl\u2212\/HCO3\u2212 exchange with CFTR in stimulated HCO3\u2212 secretion by guinea pig interlobular pancreatic duct","volume":"296","author":"Stewart","year":"2009","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_98","first-page":"465","article-title":"Cystic fibrosis transmembrane conductance regulator and SLC26 transporters in HCO3\u2212 secretion by pancreatic duct cells","volume":"59","author":"Ishiguro","year":"2007","journal-title":"Sheng Li Xue Bao"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s00424-018-2116-1","article-title":"Electrophysiological properties of anion exchangers in the luminal membrane of guinea pig pancreatic duct cells","volume":"470","author":"Andharia","year":"2018","journal-title":"Pflugers Arch."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5049","DOI":"10.1038\/sj.emboj.7601387","article-title":"Slc26a6 regulates CFTR activity in vivo to determine pancreatic duct HCO3\u2212 secretion: Relevance to cystic fibrosis","volume":"25","author":"Wang","year":"2006","journal-title":"EMBO J."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1053\/j.gastro.2011.08.039","article-title":"Trypsin reduces pancreatic ductal bicarbonate secretion by inhibiting CFTR Cl\u2212 channels and luminal anion exchangers","volume":"141","author":"Pallagi","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.1113\/JP281765","article-title":"Mislocalization of CFTR expression in acute pancreatitis and the beneficial effect of VX-661 + VX-770 treatment on disease severity","volume":"599","author":"Balla","year":"2021","journal-title":"J. Physiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3727\/000000001783987016","article-title":"Human pancreatic ductal cells: Large-scale isolation and expansion","volume":"10","author":"Gmyr","year":"2001","journal-title":"Cell Transplant."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.mce.2011.04.008","article-title":"Isolation of mouse pancreatic alpha, beta, duct and acinar populations with cell surface markers","volume":"339","author":"Dorrell","year":"2011","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1152\/japplphysiol.00043.2018","article-title":"Development of a polarized pancreatic ductular cell epithelium for physiological studies","volume":"125","author":"Rotti","year":"2018","journal-title":"J. Appl. Physiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00424-013-1333-x","article-title":"Ethanol and its non-oxidative metabolites profoundly inhibit CFTR function in pancreatic epithelial cells, which is prevented by ATP supplementation","volume":"466","author":"Hegyi","year":"2014","journal-title":"Pflugers Arch."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1053\/j.gastro.2006.11.027","article-title":"Isolation of mouse pancreatic ductal progenitor cells expressing CD133 and c-Met by flow cytometric cell sorting","volume":"132","author":"Oshima","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s10616-009-9204-1","article-title":"An improved primary culture system of pancreatic duct epithelial cells from Wistar rats","volume":"60","author":"Chen","year":"2009","journal-title":"Cytotechnology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"320","DOI":"10.21037\/atm.2020.03.75","article-title":"An improved method for the isolation and culture of rat pancreatic ductal epithelial cells","volume":"8","author":"Chang","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1038\/nprot.2013.079","article-title":"Isolation, culture and genetic manipulation of mouse pancreatic ductal cells","volume":"8","author":"Reichert","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/labinvest.2008.122","article-title":"Epithelial cells within the human pancreas do not coexpress mesenchymal antigens: Epithelial\u2013mesenchymal transition is an artifact of cell culture","volume":"89","author":"Seeberger","year":"2009","journal-title":"Lab. Investig."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/S0006-291X(02)00278-4","article-title":"Lectin as a marker for staining and purification of embryonic pancreatic epithelium","volume":"293","author":"Kobayashi","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"10876","DOI":"10.1073\/pnas.1918314117","article-title":"Single-cell resolution analysis of the human pancreatic ductal progenitor cell niche","volume":"117","author":"Qadir","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3755","DOI":"10.1172\/JCI60610","article-title":"Abnormal endocrine pancreas function at birth in cystic fibrosis ferrets","volume":"122","author":"Park","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"9355","DOI":"10.1038\/s41467-025-64774-4","article-title":"A multimodal cross-species comparison of pancreas development","volume":"16","author":"Yang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1089\/humc.2014.154","article-title":"Ferret and pig models of cystic fibrosis: Prospects and promise for gene therapy","volume":"26","author":"Yan","year":"2015","journal-title":"Hum. Gene Ther. Clin. Dev."},{"key":"ref_117","first-page":"423","article-title":"Normal human pancreas cultures display functional ductal characteristics","volume":"71","author":"Vila","year":"1994","journal-title":"Lab. Investig."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1177\/2211068214561025","article-title":"TEER measurement techniques for in vitro barrier model systems","volume":"20","author":"Srinivasan","year":"2015","journal-title":"J. Lab. Autom."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1074\/jbc.M110.136382","article-title":"Pancreatic bicarbonate secretion involves two proton pumps","volume":"286","author":"Novak","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.biocel.2006.07.011","article-title":"The inhibitory pathways of pancreatic ductal bicarbonate secretion","volume":"39","author":"Hegyi","year":"2007","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1097\/00006676-200405000-00012","article-title":"Measurement of intracellular pH in pancreatic duct cells: A new method for calibrating the fluorescence data","volume":"28","author":"Hegyi","year":"2004","journal-title":"Pancreas"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1136\/gut.2007.134361","article-title":"Effects of bile acids on pancreatic ductal bicarbonate secretion in guinea pig","volume":"57","author":"Venglovecz","year":"2008","journal-title":"Gut"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/S0039-6060(97)90041-6","article-title":"The pancreatic duct epithelium in vitro: Bile acid injury and the effect of epidermal growth factor","volume":"122","author":"Alvarez","year":"1997","journal-title":"Surgery"},{"key":"ref_124","first-page":"1763","article-title":"Long-term culture and immortalization of epithelial cells from normal adult human pancreatic ducts transfected by the E6E7 gene of human papilloma virus 16","volume":"148","author":"Furukawa","year":"1996","journal-title":"Am. J. Pathol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0002-9440(10)65567-8","article-title":"Comparative phenotypic studies of duct epithelial cell lines derived from normal human pancreas and pancreatic carcinoma","volume":"153","author":"Liu","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"4012","DOI":"10.1073\/pnas.87.10.4012","article-title":"A cystic fibrosis pancreatic adenocarcinoma cell line","volume":"87","author":"Schoumacher","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1113\/jphysiol.2008.159087","article-title":"Bestrophin expression and function in the human pancreatic duct cell line CFPAC-1","volume":"587","author":"Marsey","year":"2009","journal-title":"J. Physiol."},{"key":"ref_128","first-page":"250","article-title":"Human pancreatic adenocarcinoma line CAPAN-1 in tissue culture and the nude mouse","volume":"106","author":"Kyriazis","year":"1982","journal-title":"Am. J. Pathol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1016\/S0002-9440(10)64800-6","article-title":"Immortal human pancreatic duct epithelial cell lines with near normal genotype and phenotype","volume":"157","author":"Ouyang","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1097\/MPA.0b013e3181c15963","article-title":"Phenotype and genotype of pancreatic cancer cell lines","volume":"39","author":"Deer","year":"2010","journal-title":"Pancreas"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Khurana, N., Dodhiawala, P.B., Bulle, A., and Lim, K.H. (2020). Deciphering the role of innate immune NF-\u03baB pathway in pancreatic cancer. Cancers, 12.","DOI":"10.3390\/cancers12092675"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1158\/0008-5472.CAN-04-3502","article-title":"Predominant Bcl-XL knockdown disables antiapoptotic mechanisms","volume":"65","author":"Bai","year":"2005","journal-title":"Cancer Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1006\/geno.2000.6355","article-title":"Mapping of five new putative anion transporter genes in human and characterization of SLC26A6, a candidate gene for pancreatic anion exchanger","volume":"70","author":"Lohi","year":"2000","journal-title":"Genomics"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1023\/A:1005573024448","article-title":"Cytokine production by CAPAN-1 and CAPAN-2 cell lines","volume":"45","author":"Blanchard","year":"2000","journal-title":"Dig. Dis. Sci."},{"key":"ref_135","first-page":"881","article-title":"Cytokine regulation of constitutive production of interleukin-8 and -6 by human pancreatic cancer cell lines and serum cytokine concentrations in patients with pancreatic cancer","volume":"21","author":"Wigmore","year":"2002","journal-title":"Int. J. Oncol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s11658-024-00537-1","article-title":"Pro-inflammatory cytokines stimulate CFTR-dependent anion secretion in pancreatic ductal epithelium","volume":"29","author":"Angyal","year":"2024","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1074\/jbc.M207199200","article-title":"Ca2+ activates CFTR- and Cl\u2212-dependent HCO3\u2212 transport in pancreatic duct cells","volume":"278","author":"Namkung","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Ludovico, A., and Baroni, D. (2025). CFTR modulators counteract F508del CFTR functional defects in a pancreatic epithelial model of cystic fibrosis. Life, 15.","DOI":"10.3390\/life15081315"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/s41374-019-0300-3","article-title":"Mouse pancreatic ductal organoid culture as a relevant model to study exocrine pancreatic ion secretion","volume":"100","author":"Varga","year":"2020","journal-title":"Lab. Investig."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1007\/s00018-023-04836-2","article-title":"Human pancreatic ductal organoids with controlled polarity provide a novel ex vivo tool to study epithelial cell physiology","volume":"80","author":"Varga","year":"2023","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.cell.2014.12.021","article-title":"Organoid models of human and mouse ductal pancreatic cancer","volume":"160","author":"Boj","year":"2015","journal-title":"Cell."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1038\/s42003-024-07193-3","article-title":"Exploring human pancreatic organoid modelling through single-cell RNA sequencing analysis","volume":"7","author":"Cherubini","year":"2024","journal-title":"Commun. Biol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1038\/nprot.2016.097","article-title":"Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation","volume":"11","author":"Broutier","year":"2016","journal-title":"Nat. Protoc."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1038\/emboj.2013.204","article-title":"Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5\/R-spondin axis","volume":"32","author":"Huch","year":"2013","journal-title":"EMBO J."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1007\/s11892-019-1261-z","article-title":"Organoids from the human fetal and adult pancreas","volume":"19","author":"Balak","year":"2019","journal-title":"Curr. Diab. Rep."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1136\/gutjnl-2016-312423","article-title":"Human pluripotent stem cell-derived acinar\/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling","volume":"66","author":"Hohwieler","year":"2017","journal-title":"Gut"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jcf.2023.08.003","article-title":"Pancreatic duct organoid swelling is chloride-dependent","volume":"23","author":"Zarei","year":"2024","journal-title":"J. Cyst. Fibros."},{"key":"ref_148","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_149","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 assay on intestinal organoids from people with cystic fibrosis","volume":"23","author":"Bierlaagh","year":"2024","journal-title":"J. Cyst. Fibros."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.jcf.2019.10.022","article-title":"Forskolin-induced swelling of intestinal organoids correlates with disease severity in adults with cystic fibrosis and homozygous F508del mutations","volume":"19","author":"Berkers","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1702529","DOI":"10.1183\/13993003.02529-2017","article-title":"Stratifying infants with cystic fibrosis for disease severity using intestinal organoid swelling as a biomarker of CFTR function","volume":"52","author":"Janssens","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s13046-023-02756-4","article-title":"Macrophage\u2013organoid co-culture model for identifying treatment strategies against macrophage-related gemcitabine resistance","volume":"42","author":"Jiang","year":"2023","journal-title":"J. Exp. Clin. Cancer. Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1093\/cei\/uxae004","article-title":"Revolutionizing immune research with organoid-based co-culture and chip systems","volume":"218","author":"Papp","year":"2024","journal-title":"Clin. Exp. Immunol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.62347\/BQFH7352","article-title":"In vitro co-culture models for studying organoid\u2013macrophage interaction","volume":"14","author":"Liu","year":"2024","journal-title":"Am. J. Cancer Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s12951-022-01518-2","article-title":"Pancreatic islet organoids-on-a-chip: How far have we gone?","volume":"20","author":"Yin","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"3124","DOI":"10.1038\/s41467-019-11178-w","article-title":"Patient-derived pancreas-on-a-chip to model cystic fibrosis-related disorders","volume":"10","author":"Arora","year":"2019","journal-title":"Nat. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1279\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T15:45:16Z","timestamp":1769528716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,27]]},"references-count":156,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27031279"],"URL":"https:\/\/doi.org\/10.3390\/ijms27031279","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,27]]}}}