Aerosolised Mesenchymal Stem Cells Expressing Angiopoietin-1 Enhances Airway Repair.

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-ß) 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-ß). 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.