Researchers grow mini human lungs to imitate COVID-19 infection

The first human 'lung-in-a-dish' model, known as a lung organoid, representing all lung cell types and allowing replication of the SARS-CoV-2 virus has been produced.

Researchers at the University of California San Diego School of Medicine used surgically removed human lungs to derive adult stem cells, for the development of three lung organoids containing cells characteristic to the upper and lower airways of human lungs. SARS-CoV-2 infection of the organoids showed that upper airway cells are crucial for the virus to establish infection, whilst lower airway cells are significant for the host immune response. However, both cell types contribute to the heightened immune response observed in severe cases of COVID-19, known as a 'cytokine storm'.

'Because our... lung organoids are scalable, personalised, propagatable and cost effective, they are quite unlike any other existing model,' said Professor Pradipta Ghosh, executive director of the HUMANOID Centre of Research Excellence (CoRE) and co-leader of the study. 'This is a significant advance that can enable the modelling of lung diseases and pandemics beyond COVID-19.'

Pre-clinical animal models have been able to replicate aspects of SARS-CoV-2 infection, but have failed to develop severe clinical symptoms. The paper, published in the journal eLife, reports the creation of organoids with both upper and lower airway cells, which is crucial for emulating the cytokine storm characteristic of severe COVID-19 cases. Previous attempts to create human lung organoids have failed as not all cell types survived.

By comparing gene expression patterns, the researchers demonstrated that the organoids behave similarly to adult human lungs and replicate COVID-19 infection more accurately than any other current model. HUMANOID CoRE intends to use the lung organoids as a pre-clinical human model to identify drugs targeting both viral and host responses to infection, as well as investigating COVID-19 development.

'Our lung organoids are now ready to use to explore the uncharted territory of COVID-19, including post-COVID complications, such as lung fibrosis,' added Dr Soumita Das, founding co-director and chief scientific officer of HUMANOID CoRE and co-leader of the study. 'We have already begun to test drugs for their ability to control viral infection.'

Further to COVID-19 research, there is also potential to use the organoids to model diverse lung infections and complex diseases with no current model or cure, such as idiopathic pulmonary fibrosis.