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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 LU ; Westergren-Thorsson, Gunilla LU ; Molina-Molina, Maria ; Mercader-Barceló, Josep and Sala-Llinàs, Ernest (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
; ; ; ; ; ; ; and
organization
publishing date
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}},
}