In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis
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...
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MDPI AG
2024-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/13/2/160 |
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| author | Gabriel Escarrer-Garau Aina Martín-Medina Joan Truyols-Vives Cristina Gómez-Bellvert Linda Elowsson Gunilla Westergren-Thorsson Maria Molina-Molina Josep Mercader-Barceló Ernest Sala-Llinàs |
| author_facet | Gabriel Escarrer-Garau Aina Martín-Medina Joan Truyols-Vives Cristina Gómez-Bellvert Linda Elowsson Gunilla Westergren-Thorsson Maria Molina-Molina Josep Mercader-Barceló Ernest Sala-Llinàs |
| author_sort | Gabriel Escarrer-Garau |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T09:55:47Z |
| format | Article |
| id | doaj.art-6138692926f04a3bb494e28fe6e54efa |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T09:55:47Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-6138692926f04a3bb494e28fe6e54efa2024-01-29T13:50:28ZengMDPI AGCells2073-44092024-01-0113216010.3390/cells13020160In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary FibrosisGabriel Escarrer-Garau0Aina Martín-Medina1Joan Truyols-Vives2Cristina Gómez-Bellvert3Linda Elowsson4Gunilla Westergren-Thorsson5Maria Molina-Molina6Josep Mercader-Barceló7Ernest Sala-Llinàs8MolONE Research Group, University of the Balearic Islands (UIB), 07122 Palma, SpainiRESPIRE Research Group, Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, SpainMolONE Research Group, University of the Balearic Islands (UIB), 07122 Palma, SpainPathological Anatomy Service, Son Espases University Hospital, 07120 Palma, SpainLung Biology, Department of Experimental Medical Science, Lund University, 08908 Lund, SwedenLung Biology, Department of Experimental Medical Science, Lund University, 08908 Lund, SwedenILD Unit, Respiratory Department, University Hospital of Bellvitge-Bellvitge Biomedical Research Institute (IDIBELL), 08908 Hospitalet de Llobregat, Barcelona, SpainMolONE Research Group, University of the Balearic Islands (UIB), 07122 Palma, SpainiRESPIRE Research Group, Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, SpainLung-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.https://www.mdpi.com/2073-4409/13/2/160idiopathic pulmonary fibrosislung-resident mesenchymal stem celltransforming growth factor βbleomycininflammationextracellular matrix proteins |
| spellingShingle | Gabriel Escarrer-Garau Aina Martín-Medina Joan Truyols-Vives Cristina Gómez-Bellvert Linda Elowsson Gunilla Westergren-Thorsson Maria Molina-Molina Josep Mercader-Barceló Ernest Sala-Llinàs In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis Cells idiopathic pulmonary fibrosis lung-resident mesenchymal stem cell transforming growth factor β bleomycin inflammation extracellular matrix proteins |
| title | In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis |
| title_full | In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis |
| title_fullStr | In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis |
| title_full_unstemmed | In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis |
| title_short | In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis |
| title_sort | in vivo and in vitro pro fibrotic response of lung resident mesenchymal stem cells from patients with idiopathic pulmonary fibrosis |
| topic | idiopathic pulmonary fibrosis lung-resident mesenchymal stem cell transforming growth factor β bleomycin inflammation extracellular matrix proteins |
| url | https://www.mdpi.com/2073-4409/13/2/160 |
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