The epithelial lining cells throughout the gas exchanging regions of the lung, termed lung parenchyma, are involved prominently in a number of important human diseases: emphysema, in which epithelial tissue is lost; acute lung injury, where major epithelial injury and tissue remodeling occurs; and pulmonary fibrosis, in which scar tissue effectively replaces the epithelium. In each of these conditions the capacity to generate new alveolar epithelium, and its associated vascular bed, would be of great potential therapeutic value, but such capacity remains beyond the reach of current technology. The rationale for this goal is compelling in no small part because survival following lung transplantation is considerably less than that of other solid organs or bone marrow. The single major objective of this research application is to identify, isolate, and define the functional potential of epithelial stem cells within the human lung parenchyma. The project capitalizes on a collaborative team providing human lungs from normal and diseased subjects and an approach that has successfully identified epithelial stem/progenitor cells in normal and injured mouse lungs. If successful in translating our approach in mice to identifying and analyzing epithelial stem/progenitor cells in the human lung parenchyma, we would have made a clear next step in moving lung stem cell biology toward the clinical arena.
While symptoms of lung disease can be improved, there are currently no therapies that significantly modify the course of several major lung diseases afflicting the population of the State of California, e.g. emphysema and Idiopathic Pulmonary Fibrosis. The goal of this research is to understand the contribution of stem cells in the human lung parenchyma to lung repair and remodeling, with the belief that understanding the role of lung stem cells in repair will lead to ways to modulate their function in a protective manner. If the proposed project is successful this will be a basic but important step forward in modifying intractable lung diseases that afflict Californians.