It may be possible one day to treat several lung diseases by introducing proteins that direct lung stem cells to grow the specific cell types needed to repair the lung injuries involved in the conditions, according to new research by scientists at Boston Children's Hospital and collaborating institutions. Reporting in the January 30, 2014 issue ofCell, the researchers, led by Carla Kim, Ph.D., and Joo-Hyeon Lee, Ph.D., of the Stem Cell Research Program at Boston Children's, describe a new pathway in the lung, activated by injury, that directs stem cells to transform into specific types of cells. By enhancing this natural pathway in a mouse model, they successfully increased production of alveolar epithelial cells, which line the small sacs (alveoli) where gas exchange takes place. These cells are irreversibly damaged in diseases like pulmonary fibrosis and emphysema. By inhibiting the same pathway, the researchers ramped up production of airway epithelial cells, which become damaged in diseases affecting the lung's airways, such as asthma and bronchiolitis obliterans. Using a novel 3D culture model that mimics the environment of the lung, the researchers showed that even a single lung stem cell could be coaxed into producing alveolar and bronchiolar epithelial cells. By adding a protein known as thrombospondin-1 (TSP-1) to these cultures, they prodded the stem cells to generate alveolar cells. Dr. Kim and Dr. Lee conducted experiments using a live mouse model of fibrosis. By simply taking the endothelial cells that line the lung's many small blood vessels—which naturally produce TSP-1—and directly injecting the liquid surrounding the cultured cells into the mice, they were able to reverse the lung damage.
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