title: Limited restoration of cystic fibrosis lung epithelium in vivo with adult bone marrow-derived cells.
abstract: BACKGROUND
  Recent literature suggests that adult bone marrow-derived cells can localize to lung and acquire immunophenotypic characteristics of lung epithelial cells. We speculated this might be a potential therapeutic approach for correcting defective lung epithelium in cystic fibrosis.
  
  
  OBJECTIVE
  To determine whether adult bone marrow-derived cells containing normal cystic fibrosis transmembrane conductance regulator protein (CFTR) could repopulate lung epithelium in transgenic mice deficient in that protein.
  
  
  METHODS
  Stromal marrow cells or total marrow obtained from adult male wild-type mice were transplanted into adult female Cftr knockout mice. To increase marrow cell recruitment naphthalene was used to induce airway epithelial injury in recipient mice.
  
  
  RESULTS
  At 1 wk, 1 mo, and 3 mo after transplantation, Cftr mRNA was detected in lung homogenates of recipient mice by reverse transcription-polymerase chain reaction. Cftr mRNA was not found in either donor marrow cells or mature circulating leukocytes. In situ examination of recipient mouse lungs demonstrated rare (0.025%) chimeric airway epithelial cells, some of which (0.01%) expressed CFTR protein. Naphthalene-induced airway remodeling nonsignificantly increased the number of chimeric airway epithelial cells expressing Cftr.
  
  
  CONCLUSIONS
  These results demonstrate that adult marrow cells can be recruited to airway epithelium and induced to express Cftr in mice otherwise lacking this protein. However, the number of observed chimeric epithelial cells is small and new strategies for enhancing airway epithelial remodeling by adult bone marrow-derived cells will be necessary for correction of defective CFTR-dependent chloride transport.
authors.affiliation: 226 Health Sciences Research Facility, University of Vermont College of Medicine, Burlington, VT 05405, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Loi
authors.forename: Travis
authors.initials: T
authors.lastname: Beckett
authors.forename: Kaarin K
authors.initials: KK
authors.lastname: Goncz
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Suratt
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weiss
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D003550:Cystic Fibrosis / Q000235:genetics / Q000601:surgery*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000502:physiology; D008168:Lung / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020545:Respiratory Mucosa / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator