title: Cells of epithelial lineage are present in blood, engraft the bronchial epithelium, and are increased in human lung transplantation.
abstract: BACKGROUND
  There is a growing expectation that cell-based therapies will prove effective for a wide range of conditions including lung diseases such as cystic fibrosis. The promise of these therapies will depend largely on effective delivery and engraftment. In this study, in the setting of human lung transplantation, we sought to determine whether exogenous epithelial cells are able to engraft the transplanted organ and if cells of a similar phenotype could be detected in peripheral blood.
  
  
  METHODS
  Cells obtained from bronchial brushings and peripheral blood were analyzed via dual fluorescent in situ hybridization/fluorescent immunohistochemistry (FISH/IHC), short tandem repeat polymerase chain reaction (STR-PCR) and flow cytometry.
  
  
  RESULTS
  In 2 of 3 gender-mismatched patients we observed limited (5.9% to 6.8% by STR-PCR and 3.5% to 4% by FISH/IHC) engraftment of the bronchial epithelium by exogenous epithelial cells. Engrafting cells were CD34(-) CD15(-) CD68(-) c-Kit(-), but expressed CXCR4 on the cell surface. Cells with a similar phenotype were also identified in peripheral blood. In 8 patients, at 2 to 66 months post-transplant, 0.57 +/- 0.17% of CD14(-) peripheral blood mononuclear cells were of epithelial lineage. Almost all were CD45(+) and most expressed CXCR4 on the cell membrane. Cells of epithelial lineage were also identified in peripheral blood in healthy individuals but in much lower numbers (0.08 +/- 0.01%, p < 0.05).
  
  
  CONCLUSIONS
  Cells of epithelial lineage are detectable in peripheral blood and are able to engraft the bronchial epithelium in humans. Cell numbers are increased in lung transplantation.
authors.affiliation: Telethon Institute for Child Health Research, Subiaco, Western Australia, Australia.
authors.forename: Leigh A
authors.initials: LA
authors.lastname: May
authors.forename: Anthony
authors.initials: A
authors.lastname: Kicic
authors.forename: Paul
authors.initials: P
authors.lastname: Rigby
authors.forename: Kathryn
authors.initials: K
authors.lastname: Heel
authors.forename: Tracey-Lee
authors.initials: TL
authors.lastname: Pullen
authors.forename: Maxine
authors.initials: M
authors.lastname: Crook
authors.forename: Adrian
authors.initials: A
authors.lastname: Charles
authors.forename: Balarka
authors.initials: B
authors.lastname: Banerjee
authors.forename: David
authors.initials: D
authors.lastname: Ravine
authors.forename: Alka
authors.initials: A
authors.lastname: Saxena
authors.forename: Michael
authors.initials: M
authors.lastname: Musk
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Stick
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Chambers
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D001706:Biopsy; D001980:Bronchi / Q000166:cytology* / Q000378:metabolism; D016022:Case-Control Studies; D019070:Cell Lineage; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000378:metabolism; D016256:Lewis X Antigen / Q000378:metabolism; D016040:Lung Transplantation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology* / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; C527276:CXCR4 protein, human; D016256:Lewis X Antigen; D019718:Receptors, CXCR4; D019009:Proto-Oncogene Proteins c-kit; D017493:Leukocyte Common Antigens