{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["12"],"submitter":["Al Yazeedi S"],"pubmed_abstract":["Mechanical strain plays a significant role in lung pathophysiology. Current two-dimensional (2D) <i>in vitro</i> models fail to capture the lung's dynamic mechanical environment. We developed mechanically strained 2D and more complex three-dimensional (3D) alveolar epithelial-fibroblast co-cultures and organoids using the Flexcell cell stretching bioreactor. To do this we used readily available human A549 epithelial cells and MRC-5 lung fibroblasts to establish 2D and 3D alveolar co-cultures and collagen-I-gel-embedded organoid models in the Flexcell and then strained them at 18% amplitude, 0.4 Hz for 24 h to mimic a pathological environment. The impact of mechanical strain on cell proliferation, morphology, cytoskeletal and tight junctional protein expression, interleukin-6 and-8 (IL-6, IL-8) inflammatory cytokine release, and cell death were assessed. Mechanical strain significantly increased total cell counts in 3D co-cultures but not in 2D co-cultures, potentially signifying increased proliferation. Morphological analysis revealed a marked transition of fibroblasts into broadened shape cells under strain in the 3D co-cultures. This was in line with increased F-actin in 3D co-cultures after strain. The tight junctional protein zonula occludens-1 expression decreased after strain in all 2D and 3D models. Furthermore, exposure to strain increased the release of IL-6 and IL-8. Strain-induced cell death was also elevated across all models, particularly in 3D cultures. This study presents exploratory findings suggesting that <i>in vitro</i> mechanical multicellular alveolar models using the Flexcell system may replicate the dynamic environment of <i>in vivo</i> lung tissue. These multicellular models offer a valuable platform for investigating strain-induced cellular responses relevant to inflammatory and fibrotic mechanisms in lung diseases, particularly in exploring epithelial-mesenchymal interactions that may underlie disease progression."],"journal":["Frontiers in medicine"],"pagination":["1552803"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12401065"],"repository":["biostudies-literature"],"pubmed_title":["Dynamic mechanical stimulation of alveolar epithelial-fibroblast models using the Flexcell tension system to study of lung disease mechanisms."],"pmcid":["PMC12401065"],"pubmed_authors":["Yee L","Al Yazeedi S","Sin DD","Abokor FA","Cheung C","Guo TJF","Sohd J","Osei ET","Baher JZ"],"additional_accession":[]},"is_claimable":false,"name":"Dynamic mechanical stimulation of alveolar epithelial-fibroblast models using the Flexcell tension system to study of lung disease mechanisms.","description":"Mechanical strain plays a significant role in lung pathophysiology. Current two-dimensional (2D) <i>in vitro</i> models fail to capture the lung's dynamic mechanical environment. We developed mechanically strained 2D and more complex three-dimensional (3D) alveolar epithelial-fibroblast co-cultures and organoids using the Flexcell cell stretching bioreactor. To do this we used readily available human A549 epithelial cells and MRC-5 lung fibroblasts to establish 2D and 3D alveolar co-cultures and collagen-I-gel-embedded organoid models in the Flexcell and then strained them at 18% amplitude, 0.4 Hz for 24 h to mimic a pathological environment. The impact of mechanical strain on cell proliferation, morphology, cytoskeletal and tight junctional protein expression, interleukin-6 and-8 (IL-6, IL-8) inflammatory cytokine release, and cell death were assessed. Mechanical strain significantly increased total cell counts in 3D co-cultures but not in 2D co-cultures, potentially signifying increased proliferation. Morphological analysis revealed a marked transition of fibroblasts into broadened shape cells under strain in the 3D co-cultures. This was in line with increased F-actin in 3D co-cultures after strain. The tight junctional protein zonula occludens-1 expression decreased after strain in all 2D and 3D models. Furthermore, exposure to strain increased the release of IL-6 and IL-8. Strain-induced cell death was also elevated across all models, particularly in 3D cultures. This study presents exploratory findings suggesting that <i>in vitro</i> mechanical multicellular alveolar models using the Flexcell system may replicate the dynamic environment of <i>in vivo</i> lung tissue. These multicellular models offer a valuable platform for investigating strain-induced cellular responses relevant to inflammatory and fibrotic mechanisms in lung diseases, particularly in exploring epithelial-mesenchymal interactions that may underlie disease progression.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025","modification":"2026-05-29T22:06:51.994Z","creation":"2026-04-08T06:10:57.734Z"},"accession":"S-EPMC12401065","cross_references":{"pubmed":["40901507"],"doi":["10.3389/fmed.2025.1552803"]}}