Effects of bone marrow-derived stem cell administration in a mouse model of lung emphysema induced by cigarette smoke

According to a recent view, the net tissue loss characterizing emphysema results from an imbalance between tissue destruction and repair processes. One factor involved in the lung capacity for repair may be the ability of stem cells to replace damaged tissues. Several studies have demonstrated that following systemic administration, bone marrow−derived cell (BMSC) can localize in the lung transforming into airway or alveolar epithelial cells, interstitial cells and vascular endothelial cells. Unfortunately, whether transplanted adult stem cells are able or not to promote tissue regeneration in lung emphysema is still object of investigation. We evaluated the effects of BMSCs administration in an experimental model of pulmonary emphysema induced in mice by chronic cigarette smoke (CS) exposure. Male singenic BMSCs were transplanted by tail vein infusion in female C57Bl/6J mice, exposed for 5 months to the smoke of 3 cigarettes/day, 5 days/week. At 1 month after BMSC injection, mice were sacrificed and lung chymerism was assessed by localization of Y chromosome by FISH. The effect of BMSC administration on the development of emphysema was evaluated by morphological and morphometrical analysis (Lm, ISA). One month after BMSC injection, FISH analysis of female transplanted mice revealed engrafted male cells in the alveolar walls. These cells showed an epithelium−like morphology and were positive for cytokeratin. In sham−injected mice, chronic CS exposure resulted in disseminated foci of emphysema, a significant increase of Lm (+34%), and a significant decrease of ISA (−22%). Treatment with BMSC fully prevented all these changes. This study shows that BMSCs can repair emphysematous lung changes induced in mice by CS exposure