title: Bone marrow-derived progenitor cells in end-stage lung disease patients.
abstract: BACKGROUND
  Chronic lung diseases are marked by progressive inflammation, tissue damage and remodelling. Bone marrow-derived progenitor cells may contribute to these processes. The objectives of this study were to (1) to quantify CD45⁺Collagen-1⁺ fibrocytes and a novel epithelial-like population of bone marrow-derived cells, which express Clara Cell Secretory Protein, in patients at the time of lung transplant and (2) to evaluate mediators that may act to recruit these cells during injury.
  
  
  METHODS
  Using an observational design, progenitor cells were quantified by flow cytometry from both bone marrow (BM) and peripheral blood (PB). Migration was tested using in vitro transwell assays. Multiplex bead-based assays were used to quantify plasma cytokines.
  
  
  RESULTS
  An increase in CD45⁺Collagen-1⁺ fibrocytes was found in pulmonary fibrosis and bronchiolitis obliterans patients. Cystic fibrosis patients had an increase in CCSP⁺ cells in both the BM and PB. The proportion of CCSP⁺ cells in the BM and PB was correlated. CCSP+ cells express the chemokine receptors CCR2, CCR4, CXCR3, and CXCR4, and significantly migrated in vitro toward Stromal Derived Factor-1 (SDF-1) and Stem Cell Growth Factor-β (SCGF-β). Plasma cytokine levels differed between disease groups, with a significant correlation between SCGF-β and CCSP⁺ cells and between Monocyte Chemotactic Protein-1 and fibrocytes.
  
  
  CONCLUSIONS
  Different bone marrow-derived cells are found in various lung diseases. Increased fibrocytes were associated with fibrotic lung diseases. An increase in the novel CCSP⁺ epithelial-like progenitors in cystic fibrosis patients was found. These differences may be mediated by alterations in plasma cytokines responsible for cell recruitment.
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, North Wing, 9N - 949, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gilpin
authors.forename: Kalvin
authors.initials: K
authors.lastname: Lung
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: de Couto
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cypel
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sato
authors.forename: Lianne G
authors.initials: LG
authors.lastname: Singer
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D001989:Bronchiolitis Obliterans / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology*; D019089:Stem Cell Factor / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D014598:Uteroglobin / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; C515255:CXCL12 protein, human; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D016207:Cytokines; D019089:Stem Cell Factor; D014598:Uteroglobin
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