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oai:repisalud.isciii.es:20.500.12105/238262024-11-28T18:28:27Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16962col_20.500.12105_16967

00925njm 22002777a 4500 dc Escarrer-Garau, Gabriel author Martín-Medina, Aina author Truyols-Vives, Joan author Gómez-Bellvert, Cristina author Elowsson, Linda author Westergren-Thorsson, Gunilla author Molina-Molina, Maria author Mercader-Barceló, Josep author Sala Llinàs, Ernest author 2024-01-16 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 TGFβ. 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 TGFβ response in the expression of TGFβ, 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. Escarrer-Garau G, Martín-Medina A, Truyols-Vives J, Gómez-Bellvert C, Elowsson L, Westergren-Thorsson G, et al. In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis. Cells. 2024 Jan 16;13(2). 10.3390/cells13020160 10.3390/cells13020160 2073-4409 Cells https://hdl.handle.net/20.500.13003/20222 38247851 L2028107107 2-s2.0-85183086271 https://hdl.handle.net/20.500.12105/23826 1151954700001 In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis