In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis
(2024) In Cells 13(2). p.1-13- Abstract
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... (More)
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.
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- author
- Escarrer-Garau, Gabriel ; Martín-Medina, Aina ; Truyols-Vives, Joan ; Gómez-Bellvert, Cristina ; Elowsson, Linda LU ; Westergren-Thorsson, Gunilla LU ; Molina-Molina, Maria ; Mercader-Barceló, Josep and Sala-Llinàs, Ernest
- organization
- publishing date
- 2024-01-16
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Humans, Animals, Mice, Idiopathic Pulmonary Fibrosis, Bronchoalveolar Lavage Fluid, Bleomycin, Extracellular Matrix Proteins, Lung, Transforming Growth Factor beta
- in
- Cells
- volume
- 13
- issue
- 2
- article number
- 160
- pages
- 1 - 13
- publisher
- MDPI AG
- external identifiers
-
- scopus:85183086271
- pmid:38247851
- ISSN
- 2073-4409
- DOI
- 10.3390/cells13020160
- language
- English
- LU publication?
- yes
- id
- e4cfe440-dbe6-4b5b-9218-32ab985576e0
- date added to LUP
- 2024-01-28 12:48:07
- date last changed
- 2024-04-25 21:06:21
@article{e4cfe440-dbe6-4b5b-9218-32ab985576e0, abstract = {{<p>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.</p>}}, author = {{Escarrer-Garau, Gabriel and Martín-Medina, Aina and Truyols-Vives, Joan and Gómez-Bellvert, Cristina and Elowsson, Linda and Westergren-Thorsson, Gunilla and Molina-Molina, Maria and Mercader-Barceló, Josep and Sala-Llinàs, Ernest}}, issn = {{2073-4409}}, keywords = {{Humans; Animals; Mice; Idiopathic Pulmonary Fibrosis; Bronchoalveolar Lavage Fluid; Bleomycin; Extracellular Matrix Proteins; Lung; Transforming Growth Factor beta}}, language = {{eng}}, month = {{01}}, number = {{2}}, pages = {{1--13}}, publisher = {{MDPI AG}}, series = {{Cells}}, title = {{In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis}}, url = {{http://dx.doi.org/10.3390/cells13020160}}, doi = {{10.3390/cells13020160}}, volume = {{13}}, year = {{2024}}, }