HGF Expressing Stem Cells in Usual Interstitial Pneumonia Originate from the Bone Marrow and Are Antifibrotic

PLoS One. 2013 Jun 19;8(6):e65453. doi: 10.1371/journal.pone.0065453. Print 2013.


Background: Pulmonary fibrosis may result from abnormal alveolar wound repair after injury. Hepatocyte growth factor (HGF) improves alveolar epithelial wound repair in the lung. Stem cells were shown to play a major role in lung injury, repair and fibrosis. We studied the presence, origin and antifibrotic properties of HGF-expressing stem cells in usual interstitial pneumonia.

Methods: Immunohistochemistry was performed in lung tissue sections and primary alveolar epithelial cells obtained from patients with usual interstitial pneumonia (UIP, n = 7). Bone marrow derived stromal cells (BMSC) from adult male rats were transfected with HGF, instilled intratracheally into bleomycin injured rat lungs and analyzed 7 and 14 days later.

Results: In UIP, HGF was expressed in specific cells mainly located in fibrotic areas close to the hyperplastic alveolar epithelium. HGF-positive cells showed strong co-staining for the mesenchymal stem cell markers CD44, CD29, CD105 and CD90, indicating stem cell origin. HGF-positive cells also co-stained for CXCR4 (HGF+/CXCR4+) indicating that they originate from the bone marrow. The stem cell characteristics were confirmed in HGF secreting cells isolated from UIP lung biopsies. In vivo experiments showed that HGF-expressing BMSC attenuated bleomycin induced pulmonary fibrosis in the rat, indicating a beneficial role of bone marrow derived, HGF secreting stem cells in lung fibrosis.

Conclusions: HGF-positive stem cells are present in human fibrotic lung tissue (UIP) and originate from the bone marrow. Since HGF-transfected BMSC reduce bleomycin induced lung fibrosis in the bleomycin lung injury and fibrosis model, we assume that HGF-expressing, bone-marrow derived stem cells in UIP have antifibrotic properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Bone Marrow / physiology
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / physiology*
  • Cell Differentiation / physiology
  • Cell Separation
  • Cells, Cultured
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Idiopathic Pulmonary Fibrosis / pathology
  • Idiopathic Pulmonary Fibrosis / prevention & control*
  • Male
  • Pulmonary Alveoli / cytology*
  • Rats
  • Rats, Inbred F344
  • Stem Cell Niche*
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Stem Cells / pathology
  • Stem Cells / physiology*


  • HGF protein, human
  • Hepatocyte Growth Factor

Grants and funding

This work supported by a Swiss national science foundation grant to Thomas Geiser (SNF120-408; www.snf.ch). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.