Grant: CIHR Fellowship

In Canada 8% of all babies are born preterm, between 24 and 37 weeks of gestational age. One of the most common complications seen in these children is bronchopulmonary dysplasia (BPD). Most preterm infants need mechanical ventilation and supplemental oxygen to stay alive; unfortunately, this also damages the developing lung leading to an arrest in lung growth. Currently no treatment is available for BPD. Babies with BPD are often sent home with oxygen (O2) and continue to have respiratory diseases such as asthma or emphysema later in life. Our body contains stem cells, a pool of cells that direct growth by developing into different cell types. Stem cells may play an important role in BPD. Ventilated babies are more likely to develop BPD, if mesenchymal stem cells (MSCs) are present in lung fluid. Conversely, we showed that treatment with (liquid produced by) bone marrow or human cord-derived MSCs can prevent an O2 induced arrest in lung growth in a newborn rat model of BPD. Thus, the role of MSCs during lung injury and repair remains unclear. We will investigate whether MSCs in the newborn lung are perturbed by high O2 exposure, leading to BPD, and if they can be restored by factors secreted by healthy cord-derived MSCs. Once isolated, MSCs will be evaluated for differences in appearance, cell surface protein expression and secreted factors. We anticipate that O2 exposed lung MSCs will become pro-fibrotic (scarring) producing more of the pro-fibrotic transforming growth factor (TGF)-beta1 and TGF-beta2 molecules compared to TGF-beta3 (scarless wound healing) whereas human cord-derived MSCs will not. Furthermore, liquid from healthy human cord-derived MSCs will be added to evaluate if its therapeutic effect is mediated by normalizing the lung MSCs. A better understanding of the role and effect of stem cells will allow the development of regenerative therapies to prevent BPD in preterm children, and will also benefit adults with lung diseases.