title: HGF Expressing Stem Cells in Usual Interstitial Pneumonia Originate from the Bone Marrow and Are Antifibrotic.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pulmonary Medicine, University Hospital Bern, Bern, Switzerland ; Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Amiq
authors.initials: A
authors.lastname: Gazdhar
authors.forename: Njomeza
authors.initials: N
authors.lastname: Susuri
authors.forename: Katrin
authors.initials: K
authors.lastname: Hostettler
authors.forename: Mathias
authors.initials: M
authors.lastname: Gugger
authors.forename: Lars
authors.initials: L
authors.lastname: Knudsen
authors.forename: Michael
authors.initials: M
authors.lastname: Roth
authors.forename: Matthias
authors.initials: M
authors.lastname: Ochs
authors.forename: Thomas
authors.initials: T
authors.lastname: Geiser
mesh_terms: D000072283:A549 Cells; D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002469:Cell Separation; D002478:Cells, Cultured; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology*; D051381:Rats; D011916:Rats, Inbred F344; D055153:Stem Cell Niche; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology / Q000502:physiology*
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor