Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Acute respiratory distress syndrome (ARDS) and sepsis are among the leading causes of death in Canada, especially for critically ill patients. Both of these devastating conditions are characterized by severe acute 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 in patients. For sepsis, overwhelming widespread inflammation causes inadequate blood flow and multiorgan failure if not quickly treated. Despite decades of research, ARDS and sepsis lack specific therapies and are managed with supportive care and symptom-based treatments. The Stewart lab has completed the first clinical trial using mesenchymal stem cells as a cellular immunotherapy for septic shock; however, clinical application of cell therapies can be limited by potentially serious adverse events including formation of tumours and cellular clots. We believe that products derived from mesenchymal stem cells known as exosomes may carry anti-inflammatory and vascular protective properties. Hence, exosomes represent a potentially safer cell-free biotherapeutic intervention. The aims of this project are to evaluate the ability of exosomes to treat ARDS and sepsis in relevant preclinical models, determine the biologically active cargo that may be mediating this protective property and, given this insight, explore ways to genetically manipulate this cargo to optimize exosomes as a novel cell-free immunotherapy. The findings from this research proposal will be a crucial first step in establishing the therapeutic potential of exosomes for treating ARDS and sepsis. If genetically engineered exosomes are proven to be efficacious, our research group is ideally positioned to investigate their benefits in clinical trials, potentially improving the management of acute inflammatory conditions by supplementing supportive care with cell-free cell therapy.