Researchers at Columbia University Medical Center have successfully grown lung bud organoids in the lab that mimic the function of human lungs. The organoids can be used to create new lung disease models for studying the characteristics of a variety of lung diseases.
The human lung bud organoids include a variety of cell types, and while the 3D structures are tiny, they mimic the features of full sized lungs. The researchers have used their lung bud organoids to create models of human lung diseases in vitro for further study. Those models will hopefully allow researchers to develop treatments for currently untreatable lung diseases.
The researchers created the lung bud organoids from human pluripotent stem cells and successfully managed to recreate branching airway and alveolar structures in the lab.
The researchers said their lung bud organoids “contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture”.
The lung bud organoids were shown to react in the same way as full sized lungs to infection with respiratory syncytial virus (RSV), a common cause of lower respiratory tract infections in infants. The team reports that infection with RSV “led to swelling, detachment and shedding of infected cells into the organoid lumens, similar to what has been observed in human lungs.”
The lung bud organoids also reacted in the same way as human lungs when a pulmonary fibrosis gene mutation was introduced. “Introduction of mutation in HPS1, which causes an early-onset form of intractable pulmonary fibrosis, led to the accumulation of extracellular matrix and mesenchymal cells, suggesting the potential use of this model to recapitulate fibrotic lung disease in vitro.”
Idiopathic pulmonary fibrosis is responsible for as many as 50,000 deaths a year in the United States, with the only treatment being a lung transplant. Further study of the disease in the lung bud organoids could help researchers to develop a new treatment. There is currently no vaccine or antiviral therapy for RSV.
Dr. Hans-Willem Snoeck, professor of medicine at Columbia University Medical Center and lead author of the study, said “Organoids, created with human pluripotent or genome-edited embryonic stem cells, may be the best, and perhaps only, way to gain insight into the pathogenesis of these diseases.”
The study – A three-dimensional model of human lung development and disease from pluripotent stem cells – was published in Nature Cell Biology in March.