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

Biotechnol Lett. 2017 Aug;39(8):1269-1277. doi: 10.1007/s10529-017-2355-9. Epub 2017 May 20.

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 106 ASCs on D0 and a second dose on D7 significantly prevented tracheal obliteration 28 days after heterotopic tracheal transplantation (median of 94 vs. 16%; P < 0.01). A single dose tended towards less stenosis than controls, but did not reach statistical significance (28 vs. 94%; P = 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 = 0.058), and were better than a single local dose (16 vs. 71%; P < 0.01).

Conclusion: A second dose of ASC, given systemically after 7 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.

Keywords: Adipose stem cells; Bronchiolitis obliterans syndrome; Heterotopic tracheal transplantation.

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Bronchiolitis Obliterans / physiopathology
  • Bronchiolitis Obliterans / prevention & control*
  • Disease Models, Animal
  • Male
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Trachea* / pathology
  • Trachea* / physiopathology
  • Trachea* / transplantation