Evaluation of Simvastatin and Bone Marrow-Derived Mesenchymal Stem Cell Combination Therapy on Airway Remodeling in a Mouse Asthma Model

Abstract

Introduction: The effect of bone marrow-derived mesenchymal stem cells (BMSCs) on asthma treatment was shown in our previous study. Several studies have shown the effect of statins on BMSC preservation and migration to sites of inflammation. In this study, the effects of simvastatin and BMSC combination therapy in an ovalbumin-induced asthma model in mouse were examined.

Methods: Four groups of BALB/c mice were studied including control group (animals were not sensitized), asthma group (animals were sensitized by ovalbumin), asthma + simvastatin group (asthmatic animals were treated with simvastatin), and asthma + BMSC + simvastatin group (asthmatic animals were treated with simvastatin and BMSCs). BMSCs were isolated, characterized, labeled with BrdU, and transferred into asthmatic mice. BMSC migration, airways histopathology, and total and differential white blood cell (WBC) count in bronchoalveolar lavage (BAL) fluid were evaluated.

Results: A significant increase in the number of BrdU-BMSCs was found in the lungs of mice treated with simvastatin + BMSCs compared to mice treated with BMSCs. The histopathological changes, BAL total WBC counts, and the percentage of neutrophils and eosinophils were increased in asthma group compared to the control group. Treatment with simvastatin significantly decreased airway inflammation and inflammatory cell infiltration. Combination therapy improved all measured parameters higher than simvastatin. Goblet cell hyperplasia and subepithelial fibrosis were also decreased in combination therapy group.

Conclusion: These results indicated that simvastatin and BMSC combination therapy was superior to simvastatin therapy and BMSC therapy alone in reduction of airway remodeling and lung inflammation in the ovalbumin-induced asthma model in mouse.

Keywords: Airway remodeling; Mouse asthma model; Simvastatin; Stem cells.