Daily Archives: October 23, 2020
Tiny artificial lungs grown in a lab from adult stem cells have allowed scientists to watch how coronavirus infects the lungs in a new ‘major breakthrough‘. Researchers from Duke University and Cambridge University produced artificial lungs in two independent and separate studies to examine the spread of Covid-19. The ‘living lung‘ models minimic the tiny air sacs that take up the oxygen we breathe, known to be where most serious lung damage from the deadly virus takes place. Having access to the models to test the spread of SAS-CoV-2, the virus responsible for Covid-19, will allow researchers to test potential drugs and gain a better understanding of why some people suffer from the disease worse than others.
In both studies the 3D min-lung models were grown from stem cells that repair the deepest portions of the lungs when SARS-CoV-2 attacks – known as alveolar cells. To date, there have been more than 40 million cases of COVID-19 and almost 1.13 million deaths worldwide. The main target tissues of SARS-CoV-2, especially in patients that develop pneumonia, appear to be alveoli, according to the Cambridge team. They extracted the alveoli cells from donated tissue and reprogrammed them back to their earlier ‘stem cell‘ stage and forced them to grow into self-organising alveolar-like 3D structures that mimic the behaviour of key lung tissue. Dr Joo-Hyeon Lee, co-senior author of the Cambridge paper, said we still know surprisingly little about how SARS-CoV-2 infects the lungs and causes disease.
Representative image of three – dimensional human lung alveolar organoid produced by the Cambridge and Korean researchers to better understand SARS-CoV-2
‘Our approach has allowed us to grow 3D models of key lung tissue – in a sense, “mini-lungs” – in the lab and study what happens when they become infected.’
Duke researchers took a similar approach. The team, led by Duke cell biologist Purushothama Rao Tata, say their model will allow for hundreds of experiments to be run simultaneously to screen for new drug candidates. ‘This is a versatile model system that allows us to study not only SARS-CoV-2, but any respiratory virus that targets these cells, including influenza,‘ Tata said.
Both teams infected models with a strain of SARS-CoV-2 to better understand who the virus spreads and what happens in the lung cells in response to the disease. The Cambridge team worked with researchers from South Korea to take a sample of the virus from a patient who was infected in January after travelling to Wuhan. Using a combination of fluorescence imaging and single cell genetic analysis, they were able to study how the cells responded to the virus.
When the 3D models were exposed to SARS-CoV-2, the virus began to replicate rapidly, reaching full cellular infection just six hours after infection. Replication enables the virus to spread throughout the body, infecting other cells and tissue, explained the Cambridge research team. Around the same time, the cells began to produce interferons – proteins that act as warning signals to neighbouring cells, telling them to activate their defences. After 48 hours, the interferons triggered the innate immune response – its first line of defence – and the cells started fighting back against infection. Sixty hours after infection, a subset of alveolar cells began to disintegrate, leading to cell death and damage to the lung tissue.