title: Significant role of bone marrow-derived cells in compensatory regenerative lung growth.
abstract: BACKGROUND
  Extensive studies have attempted to clarify the contribution of bone marrow-derived cells to the regeneration of various organs, but not the lungs. We evaluated the role of bone marrow-derived cells in compensatory regenerative lung growth.
  
  
  METHODS
  We induced regenerative lung growth by left pneumonectomy in adult C57BL/6 mice. To evaluate the role of bone marrow-derived cells in lung regenerative growth, green fluorescent protein (GFP)-positive, bone marrow-transplanted chimeric mice underwent inhibition of stromal-cell-derived factor (SDF)-1α/CXCR4 signaling by 7-d continuous administration of a CXCR4 antagonist after pneumonectomy.
  
  
  RESULTS
  Left pneumonectomy resulted in a significant increase in lung dry weight, as well as an increase in lung volume, without enlargement of the alveolar air space. We observed GFP-positive cells 2.1-fold more frequently in the lungs of pneumonectomized mice versus sham-operated mice by immunohistochemistry (P = 0.001), although only a proportion of these accumulated cells possessed a pneumocyte-like appearance. Pneumonectomy induced a 1.4-fold increase in the SDF-1α level in the remaining lung at 7 d compared with sham-operated mice (P < 0.05), although pneumonectomy was not accompanied by histopathological lung injury. Blockade of SDF-1α/CXCR4 signaling resulted in a significant reduction in the accumulation of GFP-positive cells in the remaining lung at 7 d and prevented regenerative lung growth, as shown by a 10% reduction in lung dry weight at 14 d compared with control pneumonectomized mice (P < 0.05).
  
  
  CONCLUSIONS
  Bone marrow-derived cells have a significant role in compensatory regenerative lung growth in an adult mouse model. Further evaluation to clarify molecular interactions between bone marrow-derived cells and pneumocytes should prove fruitful.
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Atushi
authors.initials: A
authors.lastname: Suga
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ueda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Arata
authors.initials: A
authors.lastname: Nishimoto
authors.forename: Tohru
authors.initials: T
authors.lastname: Hosoyama
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Hamano
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000378:metabolism; D008168:Lung / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011013:Pneumonectomy; D019718:Receptors, CXCR4 / Q000378:metabolism; D012038:Regeneration
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4