The overall aim of this project is to provide a comprehensive assessment of an aerosolised cell based therapeutic delivered directly by nebuliser to the injured lung epithelium in a preclinical model of acute respiratory distress syndrome (ARDS). ARDS is currently a critically unmet clinical need and the project, if successful, will facilitate progression towards phase I/II clinical trials to treat this devastating disease.
Human mesenchymal stem cells (MSC) have been shown to be a promising cell based medicinal product in development across a broad spectrum of diseases, including bacterial pneumonia induced ARDS. Evidence is now emerging that the primary mechanisms underlying the therapeutic effect of MSC are through the secretion of soluble factors with immunosuppressive and anti-inflammatory properties, the MSC secretome. We now have preliminary data to suggest that components of the MSC secretome, conditioned medium and the extracellular vesicle fraction are efficacious in preclinical models of bacterial induced ARDS when delivered to the lung by intra-tracheal instillation.
This proposed project will assess the potential of conditioned medium and extracellular vesicles delivered by nebuliser to the injured lung. Using the preclinical ARDS model, we will assess fresh versus frozen preparations, dosage strategies, the therapeutic window and delivery to ventilated versus spontaneously breathing animals. We will capture relevant physiological outputs including arterial oxygenation, measure the respiratory acidosis and investigate modulation of the immune response. Lung function will be measured by static compliance and leukocyte infiltrate count. We will assess conditioned medium and extracellular vesicle properties pre and post nebulisation for anti-bacterial effects, pro-healing properties and inflammatory modulation in in vitro assays.
If a clear benefit is evidenced, we will use the data generated to plan and progress funding for phase I/II clinical trials. The successful conclusion of this research will open up a new treatment strategy for the managment of ARDS.