Grant: Operating Grant

Congenital Diaphragmatic Hernia (CDH) is a common birth defect affecting 1/2000 live birth. CDH occurs in the baby during pregnancy: there is a hole in the diaphragm (a sheet that separates the belly from the chest). This causes the stomach, liver or gut to move up into the chest. This makes the space in the chest very small and pushes aside the lungs and the heart. Mostly the lungs can't grow making them very small at birth. Babies with CDH have a very hard time breathing at birth and need a mechanical ventilator to stay alive. The breathing problems in these babies are due to two things: (1) Small lungs and (2) high blood pressure in the lung (also called pulmonary hypertension). Today, there is no treatment to make the small lungs grow or lower the blood pressure in the lung in babies with CDH. Because of that up to 40% of babies with CDH die; survivors have long-term health problems, mostly due to ongoing pulmonary hypertension during later childhood. The problem in these babies is that there are not enough blood vessels in their lungs. We will try to make more blood vessels in the lung to prevent or rescue pulmonary hypertension. We will do this by using a cell (the building blocks of our body) that can make new blood vessels. This cell is called an endothelial (the inner layer of the blood vessel) progenitor (a founder) cell, also known as EPC. We found that EPCs exist in the growing lung and that they help the lung grow; in CDH, we want to show that these EPCs don't work as well, and this is why the lungs are small and have high blood pressure. We will use this information to test if giving additional EPCs can make the lung grow and prevent or rescue pulmonary hypertension. Thus, we may discover a new treatment for pulmonary hypertension and improve the outcome of babies with this devastating birth defect. Our findings could also help patients with other diseases in which there is a problem with too few blood vessels such as heart attack, stroke or preeclam