A drug-responsive multicellular human spheroid model to recapitulate drug-induced pulmonary fibrosis

dc.authoridsaygili, ecem/0000-0002-8389-9079
dc.authoridAvci, Cigir Biray/0000-0001-8251-4520
dc.authoridDEVAMOGLU, Utku/0000-0002-0915-8010
dc.authoridYesil-Celiktas, Ozlem/0000-0003-4509-2212
dc.authorscopusid57201859139
dc.authorscopusid57222810035
dc.authorscopusid56798628500
dc.authorscopusid23034660400
dc.authorscopusid57212299393
dc.authorscopusid6507577336
dc.authorscopusid22837401200
dc.authorwosidsaygili, ecem/GRF-3601-2022
dc.authorwosidDevamoglu, Utku/GQY-6144-2022
dc.authorwosidBiray Avcı, Cigir/GWV-1665-2022
dc.authorwosidYesil-Celiktas, Ozlem/AAI-5713-2020
dc.contributor.authorSaygili, Ecem
dc.contributor.authorDevamoglu, Utku
dc.contributor.authorGoker-Bagca, Bakiye
dc.contributor.authorGoksel, Ozlem
dc.contributor.authorBiray-Avci, Cigir
dc.contributor.authorGoksel, Tuncay
dc.contributor.authorYesil-Celiktas, Ozlem
dc.date.accessioned2023-01-12T20:00:11Z
dc.date.available2023-01-12T20:00:11Z
dc.date.issued2022
dc.departmentN/A/Departmenten_US
dc.description.abstractAssociated with a high mortality rate, pulmonary fibrosis (PF) is the end stage of several interstitial lung diseases. Although many factors are linked to PF progression, initiation of the fibrotic process remains to be studied. Current research focused on generating new strategies to gain a better understanding of the underlying disease mechanism as the animal models remain insufficient to reflect human physiology. Herein, to account complex cellular interactions within the fibrotic tissue, a multicellular spheroid model where human bronchial epithelial cells incorporated with human lung fibroblasts was generated and treated with bleomycin (BLM) to emulate drug-induced PF. Recapitulating the epithelial-interstitial microenvironment, the findings successfully reflected the PF disease, where excessive alpha smooth muscle actin and collagen type I secretion were noted along with the morphological changes in response to BLM. Moreover, increased levels of fibrotic linked COL13A1, MMP2, WNT3 and decreased expression level of CDH1 provide evidence for the model reliability on fibrosis modelling. Subsequent administration of the Food and Drug Administration approved nintedanib and pirfenidone anti-fibrotic drugs proved the drug-responsiveness of the model.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) 2211-A National Graduate Scholarship; Turkey's Council of Higher Education (CoHE) 100/2000 PhD Scholarshipen_US
dc.description.sponsorshipE S gratefully acknowledge the Scientific and Technological Research Council of Turkey (TUBITAK) 2211-A National Graduate Scholarship and Turkey's Council of Higher Education (CoHE) 100/2000 PhD Scholarship.en_US
dc.identifier.doi10.1088/1748-605X/ac73cd
dc.identifier.issn1748-6041
dc.identifier.issn1748-605X
dc.identifier.issue4en_US
dc.identifier.pmid35617946en_US
dc.identifier.scopus2-s2.0-85131772010en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1088/1748-605X/ac73cd
dc.identifier.urihttps://hdl.handle.net/11454/77299
dc.identifier.volume17en_US
dc.identifier.wosWOS:000808283800001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherIop Publishing Ltden_US
dc.relation.ispartofBiomedical Materialsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectpulmonary fibrosisen_US
dc.subjectmulticellular spheroidsen_US
dc.subjectlung fibroblastsen_US
dc.subjectanti-fibroticsen_US
dc.subjectbleomycinen_US
dc.subjectBleomycinen_US
dc.subjectPirfenidoneen_US
dc.subjectMechanismsen_US
dc.subjectNintedaniben_US
dc.subjectInhibitoren_US
dc.subjectOrganoidsen_US
dc.subjectDiseaseen_US
dc.subjectInjuryen_US
dc.subjectBetaen_US
dc.subjectCellen_US
dc.titleA drug-responsive multicellular human spheroid model to recapitulate drug-induced pulmonary fibrosisen_US
dc.typeArticleen_US

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