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Updated: Jul 5, 2025
Isolation & Characterization of Hoechstlow CD45negative Mouse Lung Mesenchymal Stem Cells
Published on: October 26, 2011
In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic
Gabriel Escarrer-Garau1, Aina Martín-Medina2, Joan Truyols-Vives1
1MolONE Research Group, University of the Balearic Islands (UIB), 07122 Palma, Spain.
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 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.
Insights
Lung-resident mesenchymal stem cells (LR-MSC) from idiopathic pulmonary fibrosis (IPF) patients show myofibroblast traits but reduced profibrotic response. These cells may worsen lung fibrosis due to impaired repair capabilities.
Area of Science:
- Pulmonary Medicine
- Stem Cell Biology
- Fibrosis Research
Background:
- Lung-resident mesenchymal stem cells (LR-MSC) are implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis.
- LR-MSC from IPF patients exhibit senescence and altered characteristics.
- The response of IPF LR-MSC to profibrotic stimuli remains unclear.
Purpose of the Study:
- To investigate the profibrotic response of LR-MSC from IPF patients compared to controls.
- To analyze the contribution of LR-MSC to lung damage in a bleomycin-induced fibrosis model.
- To assess the in vitro response of LR-MSC to TGFβ stimulation.
Main Methods:
- Isolation and characterization of LR-MSC from IPF and control patients.
- Inoculation of LR-MSC in mice post-bleomycin instillation.
- In vitro stimulation of LR-MSC with TGFβ and analysis of gene/protein expression (aSMA, fibronectin).
Main Results:
- Mice receiving IPF LR-MSC showed poorer body weight maintenance.
- Both IPF and control LR-MSC exacerbated bleomycin-induced lung damage and inflammation.
- IPF LR-MSC had higher basal aSMA and fibronectin but attenuated TGFβ-induced gene expression.
Conclusions:
- IPF LR-MSC possess myofibroblastic features but have a diminished capacity to respond to profibrotic signals.
- In advanced IPF, LR-MSC may contribute to disease progression due to limited epithelial repair abilities.
