{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:18:32Z","timestamp":1792675112437,"version":"4.5.0"},"reference-count":78,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008385","name":"Fondazione per la Ricerca sulla Fibrosi Cistica","doi-asserted-by":"publisher","award":["FFC8#2017"],"award-info":[{"award-number":["FFC8#2017"]}],"id":[{"id":"10.13039\/501100008385","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cystic fibrosis is characterized by lung dysfunction involving mucus hypersecretion, bacterial infections, and inflammatory response. Inflammation triggers pro-fibrotic signals that compromise lung structure and function. At present, several in vitro cystic fibrosis models have been developed to study epithelial dysfunction but none of these focuses on stromal alterations. Here we show a new cystic fibrosis 3D stromal lung model made up of primary fibroblasts embedded in their own extracellular matrix and investigate its morphological and transcriptomic features. Cystic fibrosis fibroblasts showed a high proliferation rate and produced an abundant and chaotic matrix with increased protein content and elastic modulus. More interesting, they had enhanced pro-fibrotic markers and genes involved in epithelial function and inflammatory response. In conclusion, our study reveals that cystic fibrosis fibroblasts maintain in vitro an activated pro-fibrotic state. This abnormality may play in vivo a role in the modulation of epithelial and inflammatory cell behavior and lung remodeling. We argue that the proposed bioengineered model may provide new insights on epithelial\/stromal\/inflammatory cells crosstalk in cystic fibrosis, paving the way for novel therapeutic strategies.<\/jats:p>","DOI":"10.3390\/cells9061371","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T09:19:27Z","timestamp":1591089567000},"page":"1371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Intrinsic Abnormalities of Cystic Fibrosis Airway Connective Tissue Revealed by an In Vitro 3D Stromal Model"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6432-4907","authenticated-orcid":false,"given":"Claudia","family":"Mazio","sequence":"first","affiliation":[{"name":"Istituto Italiano di Tecnologia (IIT), Largo Barsanti e Matteucci 53, 80125 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura S.","family":"Scognamiglio","sequence":"additional","affiliation":[{"name":"Istituto Italiano di Tecnologia (IIT), Largo Barsanti e Matteucci 53, 80125 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"De Cegli","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli (NA), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis J. V.","family":"Galietta","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli (NA), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Di Bernardo","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli (NA), Italy"},{"name":"Department of Chemical, Materials and Industrial Production Engineering (DICMAPI) University of Naples Federico II, P. le Tecchio 80, 80125 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costantino","family":"Casale","sequence":"additional","affiliation":[{"name":"Department of Chemical, Materials and Industrial Production Engineering (DICMAPI) University of Naples Federico II, P. le Tecchio 80, 80125 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Urciuolo","sequence":"additional","affiliation":[{"name":"Department of Chemical, Materials and Industrial Production Engineering (DICMAPI) University of Naples Federico II, P. le Tecchio 80, 80125 Napoli, Italy"},{"name":"Interdisciplinary Research Centre on Biomaterials (CRIB), University of Napoli Federico II, P. le Tecchio 80, 80125 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3500-0380","authenticated-orcid":false,"given":"Giorgia","family":"Imparato","sequence":"additional","affiliation":[{"name":"Istituto Italiano di Tecnologia (IIT), Largo Barsanti e Matteucci 53, 80125 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo A.","family":"Netti","sequence":"additional","affiliation":[{"name":"Istituto Italiano di Tecnologia (IIT), Largo Barsanti e Matteucci 53, 80125 Napoli, Italy"},{"name":"Department of Chemical, Materials and Industrial Production Engineering (DICMAPI) University of Naples Federico II, P. le Tecchio 80, 80125 Napoli, Italy"},{"name":"Interdisciplinary Research Centre on Biomaterials (CRIB), University of Napoli Federico II, P. le Tecchio 80, 80125 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1039\/b924455g","article-title":"CFTR Chloride Channel in the Apical Compartments: Spatiotemporal Coupling to its Interacting Partners","volume":"2","author":"Chunying","year":"2010","journal-title":"Integr. 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