Researchers Demonstrate Growth of Yet More Lung Organoids

The tissue engineering community is making rapid progress in discovering techniques to reliably grow functional tissue structures from cells. The challenge of producing blood vessel networks remains, however, so these tissues are small in size. Any larger and the inner cells would not receive sufficient oxygen and nutrients. This is not to say that these organoids are useless - far from it. They will revolutionize many areas of research by replacing the use of animal models and greatly speeding up activities such as drug discovery and testing. Further, for many tissues the transplantation of multiple organoids to be integrated into an existing organ is a potentially viable approach to improving function and treating degenerative conditions: consider that many organs function as filtration devices or chemical factories, and these functions are only loosely connected to the present shape and location of the organ. To mention one example from recent years, there is nothing to prevent liver, pancreas, and thymus organoid tissue from usefully functioning inside lymph nodes rather than their usual location. Lungs are a less flexible situation, but it is still the case that organoids may be the basis for a useful transplantation strategy in addition to benefiting research efforts:

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, researchers have succeeded in creating three-dimensional lung organoids. 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." The researchers started with stem cells created using cells from adult lungs. They used those cells to coat sticky hydrogel beads, and then they 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, the researchers compared the lab-grown tissues with real sections of human lung. "The technique is very simple. We can make thousands of reproducible pieces of tissue that resemble lung and contain patient-specific cells."

Moreover, when researchers added certain molecular factors to the 3-D cultures, the lungs developed scars similar to those seen in the lungs of people who have idiopathic pulmonary fibrosis, something that could not be accomplished using two-dimensional cultures of these cells. Idiopathic pulmonary fibrosis is a chronic lung disease characterized by scarring of the lungs. The scarring makes the lungs thick and stiff, which over time results in 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. To study the effect of genetic mutations or drugs on lung cells, researchers have previously relied on two-dimensional cultures of the cells. But when they take cells from people with idiopathic pulmonary fibrosis and grow them on these flat cultures, the cells appear healthy. 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 their case, clinicians could collect cells from the person, turn them into stem cells, coax those stem cells to differentiate into lung cells, then use those cells in 3-D cultures. Because it's so easy to create many tiny organoids at once, researchers could screen the effect of many drugs.



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