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.
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.