3D bioengineered lung-like tissue (left) resembles adult human lung (right).
UCLA researchers have created three-dimensional lung “organoids” by coating tiny gel beads with lung-derived stem cells and then allowing them to self-assemble into the shapes of the air sacs found in human lungs. The laboratory-grown, lung-like tissue can be used to study diseases including idiopathic pulmonary fibrosis, which has traditionally been difficult to study using conventional methods.
“While we haven’t built a fully functional lung, we’ve been able to take lung cells and place them in the correct geometrical spacing and pattern to mimic a human lung,” says the study’s lead author Brigitte Gomperts, MD, associate professor of pediatric hematology/oncology and member of the UCLA Broad Stem Cell Research Center.
Idiopathic pulmonary fibrosis is a chronic lung disease characterized by scarring of the lungs. The scarring makes the lungs thick and stiff, progressively worsening shortness of breath and lack of oxygen to the brain and vital organs. After diagnosis, most people with the disease live about three-to-five years. Though researchers do not know what causes idiopathic pulmonary fibrosis in all cases, for a small percentage of people it runs in their families. Additionally, cigarette smoking and exposure to certain types of dust can increase the risk of developing the disease.
Researchers have previously relied on two-dimensional cultures of the cells to study the effect of genetic mutations or drugs on lung cells. But when they take cells from people with idiopathic pulmonary fibrosis and grow them on these flat cultures, the cells appear healthy. The inability to model idiopathic pulmonary fibrosis in the laboratory makes it difficult to study the biology of the disease and design possible treatments.
Dr. Gomperts and her colleagues started with stem cells created using cells from adult lungs. They used those cells to coat sticky hydrogel beads, then partitioned these beads into small wells, each only 7 millimeters across. Inside each well, the lung cells grew around the beads, which linked them and formed an evenly distributed three-dimensional pattern. To show that these tiny organoids mimicked the structure of actual lungs, researchers compared the lab-grown tissues with real sections of human lung. When researchers added certain molecular factors to the 3D cultures, the lungs developed scars similar to those in the lungs of people who have idiopathic pulmonary fibrosis, something that could not be accomplished using two-dimensional cultures of these cells.
Using the new lung organoids, researchers will be able to study the biological underpinnings of lung diseases, including idiopathic pulmonary fibrosis, and also test possible treatments for the diseases. To study an individual’s disease, or what drugs might work best in each case, clinicians could collect cells from the person, turn them into stem cells, coax those stem cells to differentiate into lung cells and then use those cells in 3D cultures. Because it’s easy to create many tiny organoids at once, researchers could screen the effects of many drugs.
“Development of a Three-dimensional Bioengineering Technology to Generate Lung Tissue for Personalized Disease Modeling,” Stem Cells Translational Medicine, September 15, 2016