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Stem Cell Reviews and Reports

, Volume 15, Issue 1, pp 112–125 | Cite as

Aerosolised Mesenchymal Stem Cells Expressing Angiopoietin-1 Enhances Airway Repair

  • N. S. S. Halim
  • E. S. Ch’ng
  • E. Kardia
  • S. A. Ali
  • R. Radzi
  • B. H. YahayaEmail author
Article

Abstract

Background

The aim of this study was to investigate the effects of MSCs and MSC-expressing ANGPT1 (MSC-pANGPT1) treatment via aerosolisation in alleviating the asthma-related airway inflammation in the rabbit model.

Methods

Rabbits were sensitised and challenged with both intraperitoneal injection and inhalation of ovalbumin (Ova). MSCs and MSC-pANGPT1 cells were aerosolised into rabbit lungs using the MicroSprayer® Aerosolizer Model IA-1B 48 h after injury. The post mortem was performed 3 days following cell delivery. Histopathological assessments of the lung tissues and inflammatory response were quantitatively scored following treatments.

Result(S)

Administration of aerosolised MSCs and MSC-pANGPT1 were significantly reduced inflammation of the airways (p < 0.001), as reflected by improved of structural changes such as thickness of the basement membrane, epithelium, mucosa and sub-mucosa regions. The airway inflammation score of both treatment groups revealed a significant reduction of inflammation and granulocyte infiltration at the peribronchiale and perivascular regions (p < 0.05). Administration of aerosolised MSCs alone was resulted in significant reduction in the levels of pro-inflammatory genes (IL-4 and TGF-β) while treatment with aerosolised MSC-pANGPT1 led to further reduction of various pro-inflammatory genes to the base-line values (IL4, TNF, MMP9 and TGF-β). Treatment with both aerosolised MSCs and MSC-pANGPT1 cells was also alleviated the number of airway inflammatory cells in the bronchoalveolar lavage (BAL) fluid and goblet cell hyperplasia.

Conclusion(S)

Our findings suggest that treatment with MSCs alone attenuated airway inflammation and structural changes of the airway. Treatment with MSC-pANGPT1 provided an additional effect in reducing the expression levels of various pro-inflammatory genes. Both of these treatment enhancing airway repair and therefore may provide a basis for the development of an innovative approach for the treatment and prevention of airway inflammatory diseases.

Keywords

Mesenchymal stem cells Angiopoietin-1 Aerosol delivery Airway inflammation 

Notes

Acknowledgements

This work was supported by the Universiti Sains Malaysia (USM) Research University Grant Scheme (1001/CIPPT/813059). We thank all staff and members in Animal Research Facilities and Lung Stem Cell and Gene Therapy Group, Regenerative Medicine Cluster, Advanced Medical and Dental Institute (AMDI), USM for their assistance with the animal experiments. We also thank all Advanced Diagnostic Lab staff members for helping with some parts of the histology work.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • N. S. S. Halim
    • 1
  • E. S. Ch’ng
    • 2
  • E. Kardia
    • 1
  • S. A. Ali
    • 2
  • R. Radzi
    • 3
  • B. H. Yahaya
    • 1
    Email author
  1. 1.Regenerative Medicine Cluster Advanced Medical and Dental Institute (AMDI), Universiti Sains MalaysiaPenangMalaysia
  2. 2.Oncological and Radiological Science ClusterAdvanced Medical and Dental Institute (AMDI), Universiti Sains MalaysiaPenangMalaysia
  3. 3.Animal Research FacilitiesAdvanced Medical and Dental Institute (AMDI), Universiti Sains MalaysiaPenangMalaysia

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