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.

Aerosol-based airway epithelial cell delivery improves airway regeneration and repair.

Aerosol-based cell therapy has emerged as a novel and promising therapeutic strategy for treating lung diseases. The goal of this study was to determine the safety and efficacy of aerosol-based airway epithelial cell (AEC) delivery in the setting of acute lung injury induced by tracheal brushing in rabbit. Twenty-four hours following injury, exogenous rabbit AECs were labelled with bromodeoxyuridine and aerosolized using the MicroSprayer® Aerosolizer into the injured airway. Histopathological assessments of the injury in the trachea and lungs were quantitatively scored (1 and 5 days after cell delivery). The aerosol-based AEC delivery appeared to be a safe procedure, as cellular rejection and complications in the liver and spleen were not detected. Airway injury initiated by tracheal brushing resulted in disruption of the tracheal epithelium as well as morphological damage in the lungs that is consistent with acute lung injury. Lung injury scores were reduced following 5 days after AEC delivery (AEC-treated, 0.25  ± â€…0.06 vs. untreated, 0.53  ± â€…0.05, P  < â€…0.01), and rapid clearance of haemorrhage, proteinaceous debris and hyaline membranes occurred. In the trachea, AEC delivery led to an upsurge in epithelium regeneration and repair. Re-epithelialization was significantly increased 5 days after treatment (AEC-treated, 91.07  ± â€…2.37% vs. untreated, 62.99  ± â€…7.39%, P  < â€…0.01). Our results indicate that AEC delivery helps in the regeneration and repair of the respiratory airway, including the lungs, following acute insults. These findings suggest that aerosol-based AEC delivery can be a valuable tool for future therapy to treat acute lung injury. Copyright © 2017 John Wiley & Sons, Ltd.

Aerosol-based delivery of fibroblast cells for treatment of lung diseases.

BACKGROUND: Cell-based therapy has great potential to treat patients with lung diseases. The administration of cells into an injured lung is one method of repairing and replacing lost lung tissue. However, different types of delivery have been studied and compared, and none of the techniques resulted in engraftment of a high number of cells into the targeted organ. In this in vitro study, a novel method of cell delivery was introduced to investigate the possibility of delivering aerosolized skin-derived fibroblasts. METHODS: Skin-derived fibroblasts were trypsinized and resuspended in growth medium. A syringe filled with cells (10(5) cells/mL) was attached to MicroSprayer(®) Aerosolizer, a device that can modify a liquid into an aerosol. The tip of the MicroSprayer Aerosolizer was channeled into a T25 flask containing growth medium. Survivability following aerosolization was observed on a daily basis. HeLa cells were used for comparison. The same aerosolization and culture methods were used to treat HeLa cells. RESULTS: One day following aerosolization, skin-derived fibroblasts showed no sign of vacuolation due to cell stress. They attached to the surface of the flask, indicating that most of them survived aerosolization. The surviving cells were also able to proliferate rapidly, forming a confluent monolayer of cells at day 4. In contrast, HeLa cells were unable to proliferate even after 21 days of culture. CONCLUSIONS: This study provides the first evidence that cells can be aerosolized without the risk of low cell survivability and stress. The high survival rate of fibroblast cells following aerosolization illustrates the potential for delivering of such cells in future aerosol cell-based therapy to treat lung diseases.