Intratracheal transplantation of endothelial progenitor cells attenuates smoking-induced COPD in mice

Int J Chron Obstruct Pulmon Dis. 2017 Mar 20:12:947-960. doi: 10.2147/COPD.S110781. eCollection 2017.

Abstract

Background: Endothelial progenitor cells (EPCs) might play a protective role in COPD. The aim of this study was to investigate whether intratracheal allogeneic transplantation of bone-marrow-derived EPCs would attenuate the development of smoking-induced COPD in mice.

Methods: Isolated mononuclear cells from the bone marrow of C57BL/6J mice were cultured in endothelial cell growth medium-2 for 10 days, yielding EPCs. A murine model of COPD was established by passive 90-day exposure of cigarette smoke. On day 30, EPCs or phosphate-buffered saline alone was administered into the trachea. On day 90, EPCs or 30 μL phosphate-buffered saline alone was administered into the trachea, and on day 120, inflammatory cells, antioxidant activity, apoptosis, matrix metalloproteinase (MMP)-2, and MMP-9 were measured.

Results: After EPC treatment, the lung function of the mice had improved compared with the untreated mice. Mean linear intercept and destructive index were reduced in the EPCs-treated group compared with the untreated group. In addition, the EPCs-treated mice exhibited less antioxidant activity in bronchoalveolar lavage fluid compared with the untreated mice. Moreover, decreased activities of MMP-2, MMP-9, and TUNEL-positive cells in lung tissues were detected in EPCs-treated mice.

Conclusion: Intratracheal transplantation of EPCs attenuated the development of pulmonary emphysema and lung function disorder probably by alleviating inflammatory infiltration, decelerating apoptosis, inhibiting proteolytic enzyme activity, and improving antioxidant activity.

Keywords: COPD; cigarette smoke; endothelial progenitor cells; lung function; matrix metalloproteinase; transplantation.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Apoptosis
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cells, Cultured
  • Disease Models, Animal
  • Endothelial Progenitor Cells / metabolism
  • Endothelial Progenitor Cells / transplantation*
  • Lung* / metabolism
  • Lung* / pathology
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice, Inbred C57BL
  • Phenotype
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Disease, Chronic Obstructive / prevention & control*
  • Smoke / adverse effects
  • Smoking / adverse effects*
  • Time Factors
  • Transplantation, Homologous

Substances

  • Antioxidants
  • Smoke
  • Matrix Metalloproteinase 2
  • Mmp2 protein, mouse
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse