Significant role of bone marrow–derived cells in compensatory regenerative lung growth

• Published in: The Journal of surgical research Vol. 183; no. 1; pp. 84 - 90
• Main Authors: Suga, Atushi, MD, Ueda, Kazuhiro, MD, PhD, Takemoto, Yoshihiro, MD, PhD, Nishimoto, Arata, PhD, Hosoyama, Tohru, PhD, Li, Tao-Sheng, MD, PhD, Hamano, Kimikazu, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2013
• Subjects: AMD3100; Animals; Bone marrow cells; Bone Marrow Cells - physiology; Bone Marrow Transplantation; Cell Proliferation; Chemokine CXCL12 - metabolism; Compensatory lung growth; Lung - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pneumonectomy; Receptors, CXCR4 - metabolism; Regeneration; SDF-1α; Surgery; SDF-1α; Compensatory lung growth; Pneumonectomy; Bone marrow cells; AMD3100
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2012.12.013

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.