Repeated systemic administration of adipose tissue-derived mesenchymal stem cells prevents tracheal obliteration in a murine model of bronchiolitis obliterans.

Abstract

OBJECTIVE: To investigate the effect of adipose tissue-derived mesenchymal stem cell (ASC) administered either systemically or locally in a murine model of bronchiolitis obliterans. RESULTS: When compared to controls, systemic treatment with 10ASCs on D0 and a second dose on D7 significantly prevented tracheal obliteration 28&#xa0;days after heterotopic tracheal transplantation (median of 94 vs. 16%; P&#xa0;<&#xa0;0.01). A single dose tended towards less stenosis than controls, but did not reach statistical significance (28 vs. 94%; P&#xa0;=&#xa0;0.054). On the contrary, repeated local injection was incapable of preventing tracheal obliteration when compared to a single injection or controls (37 vs. 71 vs. 87%). Two intravenous doses also tended to be better than two local injections (16 vs. 37%; P&#xa0;=&#xa0;0.058), and were better than a single local dose (16 vs. 71%; P&#xa0;<&#xa0;0.01). CONCLUSION: A second dose of ASC, given systemically after 7&#xa0;days, reduces luminal obliteration in a heterotopic tracheal transplantation model in mice, suggesting that ASC can be used to prevent obliterative bronchiolitis after lung transplantation.