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

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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.

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Acknowledgments

This study was financially supported by the Research Department of Tehran University of Medical Sciences. The results described in this paper were a part of Ph.D. student research.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Mohammadian, Hamid Reza Sadeghipour & Ravie Golchoobian

  2. Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Iraj Ragerdi Kashani & Amene Omidi

  3. Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Gila Pirzad Jahromi

  4. Department of Emergency Medical Services, Faculty of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Amir Kavian Nejad

  5. Neurogenic Inflammation Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohammad Hossein Boskabady

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  1. Maryam Mohammadian
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  2. Hamid Reza Sadeghipour
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  3. Iraj Ragerdi Kashani
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  8. Mohammad Hossein Boskabady
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Correspondence to Mohammad Hossein Boskabady.

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Mohammadian, M., Sadeghipour, H.R., Kashani, I.R. et al. Evaluation of Simvastatin and Bone Marrow-Derived Mesenchymal Stem Cell Combination Therapy on Airway Remodeling in a Mouse Asthma Model. Lung 194, 777–785 (2016). https://doi.org/10.1007/s00408-016-9884-1

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  • DOI: https://doi.org/10.1007/s00408-016-9884-1

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