Grant: Operating Grant

When people become critically ill, such as during severe infection, their lungs often fail - this is termed "Acute Respiratory Distress Syndrome" (ARDS). ARDS is common, and often fatal, with over 30,000 new sufferers annually in Canada. Mortality remains high at 4 in 10 ARDS sufferers, and is comparable to that seen from HIV infection, breast cancer, and asthma. ARDS survivors subsequently experience a poorer quality of life. There is no pharmacologic therapy for ARDS and novel therapies are urgently required. Mesenchymal Stromal Cells (MSCs) offer hope for ARDS patients, and early findings in disease models are promising. However, much remains unknown, particular in regard to our understanding of how MSCs work. A greater understanding of how these cells work should generate insights that will help us to develop a modified MSC that will be more effective for patients with ARDS. We wish to focus on understanding how MCSs can reduce infection induced lung damage, and how they enhance the reparative process following injury, and apply these insights to developing an enhanced MSC therapy. This project is designed to address these questions, so that we can move forward to determining whether MSC's are effective in actual ARDS sufferers. We aim to focus on how these cells help fight infection, and help repair the damaged lung. We aim to first understand how the MSC exerts these effects, then identify approached that might be useful to make the cells even better at fighting infection and repairing the lung. We will then use these insights to develop an enhanced MSC, and we will then test and refine this therapy in models of disease of increasing complexity that most closely approximate human ARDS. If our efforts are successful, we will then use this information to design a clinical study to test the ability of this advanced MSC to save the lives of patients with ARDS, improve the quality of life of survivors, and potentially reduce healthcare costs.