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Levis, Jamie

Pathology

2006

MS

Recent studies have suggested that adult bone marrow-derived cells can migrate to the lung and modulate lung injury. Although the mechanisms that underlie this phenomenon are not clearly understood, there is evidence that alterations of injury patterns may be related to normalization of inflammation and/or repopulation of the lung with marrow-derived cells. Inhalation of asbestos fibers elicits epithelial cell proliferation, pulmonary inflammation, and fibrosis. The objective of this study was to assess the effect of systemic administration of bone marrow-derived cells on these outcomes using a murine model of fibrogenesis. Inhalation of asbestos for 3, 9, and 40 days resulted in increases in epithelial cell proliferation, lung inflammation, and peribronchiolar/interstitial fibrosis, respectively. Lung injury progressed following cessation of a 3 day exposure. Following myeloablation and bone marrow reconstitution, mice exposed to asbestos via inhalation for 3, 9, and 40 days showed recruitment of marrow-derived cells to the lungs and significant decreases in epithelial cell proliferation, lung inflammation and peribronchiolar/interstitial fibrosis. Administration of marrow-derived stromal cells to mice with an intact hematopoietic system immediately following inhalation of asbestos for 3 days resulted in alterations in the inflammatory and injury indices in bronchoalveolar lavage fluid (BALF), but did not result in localization of donor-derived cells to the lungs of these mice. The cellular mechanisms which underlie the observed reductions of fibrosis, inflammation and epithelial mitogenesis may be important in the treatment and prevention of fibroproliferative disorders of the lung. In addition, systemic administration of bone marrow cells may be an approach for the treatment of these diseases.