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Aerosolised Mesenchymal Stem Cells Expressing Angiopoietin-1 Enhances Airway Repair

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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.

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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.

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Authors and Affiliations

  1. Regenerative Medicine Cluster, Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, 13200, Bertam, Penang, Malaysia

    N. S. S. Halim, E. Kardia & B. H. Yahaya

  2. Oncological and Radiological Science Cluster, Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, 13200, Bertam, Penang, Malaysia

    E. S. Ch’ng & S. A. Ali

  3. Animal Research Facilities, Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, 13200 Bertam, Penang, Malaysia

    R. Radzi

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Correspondence to B. H. Yahaya.

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Halim, N.S.S., Ch’ng, E.S., Kardia, E. et al. Aerosolised Mesenchymal Stem Cells Expressing Angiopoietin-1 Enhances Airway Repair. Stem Cell Rev and Rep 15, 112–125 (2019). https://doi.org/10.1007/s12015-018-9844-7

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