• DOI:10.1164/rccm.200809-1390OC
• Corpus ID: 17297152

Prominin-1/CD133+ lung epithelial progenitors protect from bleomycin-induced pulmonary fibrosis.

@article{Germano2009Prominin1CD133LE,
  title={Prominin-1/CD133+ lung epithelial progenitors protect from bleomycin-induced pulmonary fibrosis.},
  author={David J. Germano and Przemysław Błyszczuk and Alan Valaperti and Gabriela Kania and Stephan Dirnhofer and Ulf Landmesser and Thomas F. L{\"u}scher and Lukas Hunziker and Henryk Zulewski and Urs Eriksson},
  journal={American journal of respiratory and critical care medicine},
  year={2009},
  volume={179 10},
  pages={
          939-49
        }
}

• D. Germano, P. Błyszczuk, +7 authors U. Eriksson
• Published 15 May 2009
• Biology, Medicine
• American journal of respiratory and critical care medicine

RATIONALE
The mouse model of bleomycin-induced lung injury offers an approach to study idiopathic pulmonary fibrosis, a progressive interstitial lung disease with poor prognosis. Progenitor cell-based treatment strategies might combine antiinflammatory effects and the capacity for tissue repair.

OBJECTIVES
To expand progenitor cells with reparative and regenerative capacities and to evaluate their protective effects on pulmonary fibrosis in vivo.

METHODS
Prominin-1/CD133(+) epithelial progenitor cells (PEPs) were expanded from adult mouse lungs after digestion and culture of distal airways. Lung fibrosis was induced in C57Bl/6 mice by instillation of bleomycin. Two hours later, animals were transplanted with PEPs. Inflammation and fibrosis were assessed by immunohistochemistry, bronchoalveolar lavage fluid differentials, and real-time polymerase chain reaction.

MEASUREMENTS AND MAIN RESULTS
PEPs expanded from mouse lungs were of bone marrow origin, coexpressed stem and hematopoietic cell markers, and differentiated in vitro into alveolar type II surfactant protein-C(+) epithelial cells. In bleomycin-challenged mice, intratracheally injected PEPs engrafted into the lungs and differentiated into type II pneumocytes. Furthermore, PEPs suppressed proinflammatory and profibrotic gene expression, prevented the recruitment of inflammatory cells, and protected bleomycin-challenged mice from pulmonary fibrosis. Mechanistically, the protective effect depended on upregulation of inducible nitric oxide synthase in PEPs and nitric oxide-mediated suppression of alveolar macrophage proliferation. Accordingly, PEPs from iNOS(-/-) but not iNOS(+/+) mice failed to protect from bleomycin-induced lung injury.

CONCLUSIONS
The combined antiinflammatory and regenerative capacity of bone marrow-derived pulmonary epithelial progenitors offers a promising approach for development of cell-based therapeutic strategies against pulmonary fibrosis.