Pneumonia is a common disease accounting for 5% of deaths in Ireland and is the most common cause of acute lung injury and acute respiratory distress syndrome (ALI/ARDS) where there currently remains no specific therapy. This frontier multidisciplinary project seeks to comprehensively evaluate the efficacy of using human mesenchymal stem cells (hMSCs) with and without β-glucan derived from a broad range of medicinal fungi (screened ex vivo) for the novel treatment of pneumonia infections caused by mixed (polymicrobial) clinical isolates from BAL patient samples (K. pneumoniae, P. aerugniosa, E. coli and S. aureus including MRSA). hMSc ± β-glucan secretome bactericidal and immunomodulating activities will be first characterised ex vivo that includes using human phagocytic leukocytes, neutrophils and primary small airway epithelial cells. Specific involvement of antimicrobial and immunomodulating substances ex vivo will be elucidated in addition to determining the synergistic role (if any) between use of MSCs and β-glucan in fighting polymicrobial-mediated ALI/ARDS. Mechanisms of possible adaptive resistance (if any) to MSC ±β-glucans exposure will be determined. The aforementioned will guide important in vivo antimicrobial and immunomodulatory studies using BAL patient samples to formulate the best therapeutic approach for the treatment of ALI/ARDs. Rodents will be infected with BAL derived clinical samples (comprising single and combined isolates) in tandem with prior and/or simultaneous MSC ±β-glucan treatments in order to ascertain their specific involvement in eliminating or preventing ALI/ARDS. The role of key antimicrobial and immunomodulatory substances in this in vivo model will be ascertained. The PI, applicants and collaborators are recognised leaders in their respective fields of study; the aim of this project is strongly aligned with the strategic research strengths and direction of AIT and NUI Galway where the envisaged outcomes will have a profound influence on patient care and quality of life.
