Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Babies born too early have lungs that are not fully developed. To survive, they often need extra oxygen and breathing machines. While life-saving, these treatments can also damage the fragile lungs and cause inflammation. This can lead to a long-term condition called bronchopulmonary dysplasia (BPD), which lacks effective treatment. A promising new approach utilizes mesenchymal stromal cells (MSCs), a type of adult stem cell tested in many diseases. In animal studies, MSCs reduce inflammation and help lungs heal. Our team's Phase I clinical trial, called Helping Underdeveloped Lungs with Cells-1 (HULC-1), showed that MSC treatment is safe and feasible in premature infants. A larger Phase 2 trial, HULC-2, will now test whether MSCs can prevent or treat BPD. However, we still do not fully understand how MSCs help repair the lung, or how the injured lung environment might change their healing effect once administered to a baby. To answer these questions, we focus on extracellular vesicles (EVs). These are "messages" that cells release, carrying information about what is happening inside them. EVs act like "fingerprints" of cell activity and can be collected from fluid that is routinely suctioned from a baby's breathing tube, requiring no extra procedures. Our research has three goals: (1) create a "map" linking EVs to the lung cell type they come from (2) test how fluids from the lungs of premature babies affect MSCs in the lab to learn whether the injured environment changes their healing potential, and (3), apply this knowledge to EV samples from babies enrolled in the HULC-2 trial, to help us understand how MSC treatment reshapes the lung environment. By combining these studies, we will uncover how MSCs and premature lungs interact, and how EVs can serve as a safe, non-invasive tool to monitor lung health. This knowledge will advance new strategies to study, prevent, and treat BPD.