{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:57:33Z","timestamp":1790377053193,"version":"4.1.0"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["F31HL164005-02"],"award-info":[{"award-number":["F31HL164005-02"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["1R35HL135816-01"],"award-info":[{"award-number":["1R35HL135816-01"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["P30DK072482"],"award-info":[{"award-number":["P30DK072482"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["R01HL152246"],"award-info":[{"award-number":["R01HL152246"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["ROWE19RO"],"award-info":[{"award-number":["ROWE19RO"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Cystic fibrosis (CF) is a genetic disease hallmarked by aberrant ion transport that results in delayed mucus clearance, chronic infection, and progressive lung function decline. Several animal models have been developed to study the airway anatomy and mucus physiology in CF, but they are costly and difficult to maintain, making them less accessible for many applications. A more available CFTR<jats:sup>\u2212\/\u2212<\/jats:sup> rat model has been developed and characterized to develop CF airway abnormalities, but consistent dosing of pharmacologic agents and longitudinal evaluation remain a challenge. In this study, we report the development and characterization of a novel <jats:italic>ex vivo<\/jats:italic> trachea model that utilizes both wild type (WT) and CFTR<jats:sup>\u2212\/\u2212<\/jats:sup> rat tracheae cultured on a porcine gelatin matrix. Here we show that the <jats:italic>ex vivo<\/jats:italic> tracheae remain viable for weeks, maintain a CF disease phenotype that can be readily quantified, and respond to stimulation of mucus and fluid secretion by cholinergic stimulation. Furthermore, we show that <jats:italic>ex vivo<\/jats:italic> tracheae may be used for well-controlled pharmacological treatments, which are difficult to perform on freshly excised trachea or <jats:italic>in vivo<\/jats:italic> models with this degree of scrutiny. With improved interrogation possible with a durable trachea, we also established firm evidence of a gland secretion defect in CFTR<jats:sup>\u2212\/\u2212<\/jats:sup> rat tracheae compared to WT controls. Finally, we demonstrate that the <jats:italic>ex vivo<\/jats:italic> tracheae can be used to generate high mucus protein yields for subsequent studies, which are currently limited by <jats:italic>in vivo<\/jats:italic> mucus collection techniques. Overall, this study suggests that the <jats:italic>ex vivo<\/jats:italic> trachea model is an effective, easy to set up culture model to study airway and mucus physiology.<\/jats:p>","DOI":"10.1371\/journal.pone.0293367","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T17:28:17Z","timestamp":1698168497000},"page":"e0293367","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["An ex vivo rat trachea model reveals abnormal airway physiology and a gland secretion defect in cystic fibrosis"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1444-6463","authenticated-orcid":true,"given":"Elex","family":"Harris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Easter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janna","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Krick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarrod","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9045-0133","authenticated-orcid":true,"given":"Steven M.","family":"Rowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"issue":"6","key":"pone.0293367.ref001","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.1074\/jbc.275.6.3729","article-title":"Cystic fibrosis transmembrane conductance regulator. 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