Enhancing the antimicrobial efficacy of mesenchymal stem cells (MSCs) for eliminating sepsis induced acute lung injury (ALI) using a novel combination of immune-stimulants

Despite advances in medicine, pneumonia is still 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 where there currently remains no specific therapy. Studies carried out by this and other research groups have recently shown that bone-marrow derived mesenchymal stem cells (MSCs) are able to reduce mortality and bacterial sepsis in rodent infection models. However, the potential therapeutic value of cell-based patient therapy with MSCs remains undefined which is attributed in part to a dearth in critical knowledge underpinning the complex mechanisms responsible for these beneficial effects in vivo. This study will also investigate the novel synergistic use of beta-glucans derived from medicinal mushrooms as these have been shown to similarly modulate the innate immune system to fight sepsis. The aim of this frontier project is to evaluate and to define the antimicrobial properties of MSCs (beta-glucans derived from medicinal fungi) on clinically-derived bacteria polymicrobial that cause pneumonia. We propose to investigate MSC beta-glucans both ex vivo and in a pre-clinical study with the view to formulating the best therapeutic approach for resolving pathogen-mediated ALI. MSCs produced from the Centre for Cell Manufacturing Ireland (NUI Galway) will be comprehensively examined for antibacterial activity against clinical pneumonia isolates and for MSCs ability to augment the human immune response to fight sepsis. The applicants are recognised leaders in their respective fields of study, have a rich history of fruitful collaboration, and have the desired commensurate mix of expertise to comprehensively deliver on this project. This next-generation therapeutic-project is strongly aligned with national prioritisation for research and with the strategic direction of AIT and NUI Galway where envisaged outcomes will have a profound influence on patient care and quality of life.

Award Date
20 June 2014
Award Value
€285,246
Principal Investigator
Professor Neil Rowan
Host Institution
Athlone Institute of Technology
Scheme
Health Research Awards