Researchers at the University of California, San Diego (UCSD) have grown miniature human lungs in a lab dish that they say come the closest to mimicking the real thing—complete with all the myriad cell types found in the body.
The small organoids of human tissue could help rapidly iterate the testing of new treatments for respiratory and infectious diseases including COVID-19 by allowing scientists to explore their preliminary effects without needing a full study.
“This human disease model will now allow us to test drug efficacy and toxicity and reject ineffective compounds early in the process, at ‘Phase 0,’ before human clinical trials begin,” Pradipta Ghosh, M.D., professor at the UCSD School of Medicine, said in a statement.
In a paper published in the journal eLife, Ghosh and her colleagues described how they built three lines of organoids out of adult stem cells, taken from the surgically removed organ of a patient with lung cancer—and showed that infecting those models with the coronavirus could replicate real-world cases. The mini-lungs also helped reveal how the organ’s different types of cells work when faced with an infection.
The researchers were able to produce the cells that make up both the lungs’ upper and lower airways as well as the specialized cells that line the alveoli and help exchange oxygen and carbon dioxide. They found that the upper airway cells help the virus establish an infection, while the lower cells aid in the body’s immune response.
Both types can also feed into the dangerously hyperactive immune response known as a cytokine storm, which has been seen in some cases of COVID-19.
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A separate team of computational researchers evaluated the organoids’ gene expression patterns and compared them to the records of patients who died of the disease. They found the mini-lungs behaved similarly to real-world infections better than other models, such as those including only one type of cell or derived from other methods.
“Our lung organoids are now ready to use to explore the uncharted territory of COVID-19, including post-COVID complications such as lung fibrosis,” said Soumita Das, founding co-director of UCSD’s HUMANOID Center of Research Excellence, which focuses on cell organoid models and drug discovery.
“We have already begun to test drugs for their ability to control viral infection—from entry to replication to spread—the runaway immune response that is so often fatal, and lung fibrosis,” Das said.