According to study results published in the January 30th issue of Cell, researchers from the Stem Cell Research Program at Boston Children’s Hospital have found a new pathway in the lung, activated by injury, that directs stem cells to transform into specific types of cells.
The study reveals that by enhancing this natural pathway in a mouse model, the researchers successfully increased production of alveolar epithelial cells, which line the alveoli, where gas exchange takes place. These cells are irreversibly damaged in diseases such as 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 3D culture model that mimics the environment of the lung, the researchers demonstrated that even a single lung stem cell could be coaxed into producing alveolar and bronchiolar epithelial cells. By adding the protein thrombospondin-1 (TSP-1) to these cultures, they prodded the stem cells to generate alveolar cells.
According to the study, Kim and Lee conducted experiments using a live mouse model of fibrosis. The process called for 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. By doing this, the researchers were able to reverse the lung damage.
Conversely, when the team used lung endothelial cells that lacked TSP-1 in the 3D cultures, the stem cells produced more airway cells. In live mice engineered to lack TSP-1, airway repair was enhanced after injury.
“When lung cells are injured, there seems to be a cross talk between the damaged cells, the lung endothelial cells and the stem cells,” said Joo-Hyeon Lee, PhD.
“We think that lung endothelial cells produce a lot of repair factors besides TSP-1,” added Kim Carla Kim, PhD, the paper’s senior author. “We want to find all these molecules, which could provide additional therapeutic targets.”