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oai:recercat.cat:2445/2249742026-04-08T13:55:57Zcom_2072_1057col_2072_478916col_2072_478917

In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis Escarrer Garau, Gabriel Martín Medina, Aina Truyols Vives, Joan Gómez Bellvert, Cristina Elowsson, Linda Westergren Thorsson, Gunilla Molina Molina, María Mercader Barceló, Josep Sala Llinàs, Ernest Fibrosi pulmonar Malalties pulmonars obstructives cròniques Farmacologia respiratòria Pulmonary fibrosis Chronic obstructive pulmonary diseases Pulmonary pharmacology Lung-resident mesenchymal stem cells (LR-MSC) are thought to participate in idiopathic pulmonary fibrosis (IPF) by differentiating into myofibroblasts. On the other hand, LR-MSC in IPF patients present senescence-related features. It is unclear how they respond to a profibrotic environment. Here, we investigated the profibrotic response of LR-MSC isolated from IPF and control (CON) patients. LR-MSC were inoculated in mice 48 h after bleomycin (BLM) instillation to analyze their contribution to lung damage. In vitro, LR-MSC were exposed to TGF beta. Mice inoculated with IPF LR-MSC exhibited worse maintenance of their body weight. The instillation of either IPF or CON LR-MSC sustained BLM-induced histological lung damage, bronchoalveolar lavage fluid cell count, and the expression of the myofibroblast marker, extracellular matrix (ECM) proteins, and proinflammatory cytokines in the lungs. In vitro, IPF LR-MSC displayed higher basal protein levels of aSMA and fibronectin than CON LR-MSC. However, the TGF beta response in the expression of TGF beta, aSMA, and ECM genes was attenuated in IPF LR-MSC. In conclusion, IPF LR-MSC have acquired myofibroblastic features, but their capacity to further respond to profibrotic stimuli seems to be attenuated. In an advanced stage of the disease, LR-MSC may participate in disease progression owing to their limited ability to repair epithelial damage. 2025-12-16T11:43:51Z 2025-12-16T11:43:51Z 2024-01-16 2025-12-05T11:33:51Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2073-4409 https://hdl.handle.net/2445/224974 38247851 eng Reproducció del document publicat a: https://doi.org/10.3390/cells13020160 Cells, 2024, vol. 13, num. 2, 160 https://doi.org/10.3390/cells13020160 cc-by (c) Escarrer Garau, Gabriel et al., 2024 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess 13 p. application/pdf MDPI AG Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))