Grant: Doctoral: Vanier Canada Graduate Scholarships

Acute respiratory distress syndrome (ARDS) and sepsis are among the leading causes of death in Canada, especially for critically ill patients. These devastating conditions are characterized by severe inflammation in response to an insult or infection. In ARDS, inflammation localized to the lungs impairs normal gas exchange, which can lead to respiratory failure. For sepsis, overwhelming inflammation throughout the body leads to failure of vital organs such as the kidney, heart, and brain if not quickly treated. Despite decades of research, there are no specific therapies for ARDS and sepsis and current treatment consists mainly of supportive care. The Stewart Lab has completed the first clinical trial using a stem cell type called mesenchymal stem cells to reduce damaging inflammation in septic shock. However, delivery of cells can potentially cause serious adverse events including formation of tumours and blood clots. I believe that small membrane-bound particles released by mesenchymal stem cells, known as exosomes, may have similar beneficial effects in inflammatory diseases, without the risks of cell delivery. Hence, exosomes represent a potentially safer "cell-free" treatment option. The aims of this project are to evaluate the ability of exosomes to treat ARDS and sepsis in relevant animal models, to identify the biologically active cargo contained in these tiny particles that may be mediating this protective property and, given this insight, explore ways to genetically modify this cargo to enhance the therapeutic effects of exosomes. The findings from this research proposal will be a crucial first step in establishing the therapeutic potential of exosomes for treating acute inflammation. If exosomes are proven beneficial in ARDS and sepsis, our research group is ideally positioned to move this potentially life-saving treatment into clinical trials, and provide a novel approach for treating these vulnerable patient populations in Canada and around the world.