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Updated: Apr 25, 2026
Isolation of CD146+ Resident Lung Mesenchymal Stromal Cells from Rat Lungs
Published on: June 17, 2016
ABCG2pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling
Shennea Marriott1, Rubin S Baskir2, Christa Gaskill1
1Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University, Nashville, Tennesse;
Abstract:
Genesis of myofibroblasts is obligatory for the development of pathology in many adult lung diseases. Adult lung tissue contains a population of perivascular ABCG2(pos) mesenchymal stem cells (MSC) that are precursors of myofibroblasts and distinct from NG2 pericytes. We hypothesized that these MSC participate in deleterious remodeling associated with pulmonary fibrosis (PF) and associated hypertension (PH). To test this hypothesis, resident lung MSC were quantified in lung samples from control subjects and PF patients. ABCG2(pos) cell numbers were decreased in human PF and interstitial lung disease compared with control samples. Genetic labeling of lung MSC in mice enabled determination of terminal lineage and localization of ABCG2 cells following intratracheal administration of bleomycin to elicit fibrotic lung injury. Fourteen days following bleomycin injury enhanced green fluorescent protein (eGFP)-labeled lung MSC-derived cells were increased in number and localized to interstitial areas of fibrotic and microvessel remodeling. Finally, gene expression analysis was evaluated to define the response of MSC to bleomycin injury in vivo using ABCG2(pos) MSC isolated during the inflammatory phase postinjury and in vitro bleomycin or transforming growth factor-β1 (TGF-β1)-treated cells. MSC responded to bleomycin treatment in vivo with a profibrotic gene program that was not recapitulated in vitro with bleomycin treatment. However, TGF-β1 treatment induced the appearance of a profibrotic myofibroblast phenotype in vitro. Additionally, when exposed to the profibrotic stimulus, TGF-β1, ABCG2, and NG2 pericytes demonstrated distinct responses. Our data highlight ABCG2(pos) lung MSC as a novel cell population that contributes to detrimental myofibroblast-mediated remodeling during PF.
Insights
Adult lung mesenchymal stem cells (MSCs) expressing ABCG2 contribute to myofibroblast formation in pulmonary fibrosis. These cells are reduced in fibrotic lungs but increase and promote remodeling after injury, highlighting their role in lung disease progression.
Area of Science:
- Pulmonary Medicine
- Stem Cell Biology
- Pathology
Background:
- Myofibroblast generation is crucial for adult lung disease pathology.
- Adult lung tissue harbors perivascular ABCG2-positive mesenchymal stem cells (MSCs) that are myofibroblast precursors.
- These MSCs are distinct from NG2 pericytes.
Purpose of the Study:
- To investigate the role of lung MSCs in the detrimental remodeling associated with pulmonary fibrosis (PF) and pulmonary hypertension (PH).
- To quantify resident lung MSCs in control and PF patient samples.
- To determine the lineage and localization of ABCG2-positive cells following bleomycin-induced lung injury in mice.
Main Methods:
- Quantification of ABCG2-positive cells in human lung samples from controls and PF patients.
- Genetic labeling of lung MSCs in mice for lineage tracing after bleomycin administration.
- Gene expression analysis of isolated ABCG2-positive MSCs in vivo and in vitro following bleomycin or TGF-β1 treatment.
Main Results:
- ABCG2-positive cell numbers were decreased in human PF and interstitial lung disease samples compared to controls.
- Following bleomycin injury in mice, eGFP-labeled lung MSC-derived cells increased and localized to fibrotic and remodeled microvessel areas.
- In vitro, TGF-β1 treatment induced a profibrotic myofibroblast phenotype in MSCs, with distinct responses observed in ABCG2-positive cells and NG2 pericytes.
Conclusions:
- ABCG2-positive lung MSCs are a novel cell population implicated in detrimental myofibroblast-mediated remodeling during pulmonary fibrosis.
- These findings suggest a significant contribution of lung MSCs to the pathogenesis of PF and associated complications.
