Grant: CIHR Fellowship

Lungs are made of pipes (conducting airways) that deliver oxygen to millions of air sacs (alveoli) where oxygen is taken up by the blood and distributed to the rest of the body. These air sacs are coated with surfactant produced by lung cells. Surfactant keeps the air sacs wide open to insure exchange of oxygen. Surfactant is made out of a mixture of proteins and lipids. Amongst these surfactant proteins (SP), SP-B and SP-C decrease lung surface tension to keep the alveoli open. Unfortunately, there are rare, but lethal genetic diseases in which SP-B is abnormal. Babies born with SP-B deficiency have trouble breathing at birth because the alveoli are crumpled and can't open. These babies usually die or develop lung fibrosis (scarring). Currently, there is no therapy. Our body contains stem cells, a pool of cells that have the ability to become any type of cell (i.e. bone, muscle or lung cell). The "best" stem cells known so far are the embryonic stem cells (ESCs) because they can become any type of cells in the body, but there are ethical, social and technical issues with ESCs. A major discovery was achieved in 2006 (and rewarded with the Nobel Prize in 2012) when researchers showed that one could turn a skin cell into an embryonic-like stem cell. These cells are called "induced pluripotent stem cells" or iPSCs. It is now possible to make stem cells from any patient with a genetic disease. The objective of our project is to correct the genetic defect in iPSCs from patients suffering from SP-B deficiency. We will first test if we can fix the mutation in iPSCs from patients with SP-B deficiency. In a second step, we will take human iPSCs, turn these into lung cells that produce surfactant, and deliver these to SP-B deficient mice. Then we will verify if these cells are safe and restore normal breathing and produce surfactant. The novel technologies represent a promising and innovative way to discover a new treatment for these devastating genetic disorders.