Lungs in a test tube
Alveoli are thin air sacs, similar to a balloon. Their damage leads to the development of pneumonia and acute respiratory failure, which is the main cause of death in patients with Covid-19. But in studies of this disease, scientists lacked experimental models that mimic human lung tissue.
A group of researchers from Duke University, led by Purushotham Rao Tata, has developed lung organoids, the so-called mini-lungs in vitro. The organoids were grown from alveolar epithelial type 2 (AT2) cells, which are essentially stem cells and are able to repair the deepest lung tissues.
Earlier research at Duke University showed that just one AT2 cell can produce millions of cells that assemble into hollow circular structures similar to alveoli. But for cultivation, complex components were required, for example, cow blood serum. The Tata Group has taken on the serious task of predicting and testing many combinations of chemically pure factors that could replace cow's whey.
The result was a purely human organoid without any auxiliary cells. Mini-lungs grown in vitro will increase research productivity, as they will help to conduct hundreds of experiments simultaneously to screen drug candidates or to identify self-defense chemicals produced by lung cells in response to infection.
A mini organoid of the lung with alveoli.
The authors consider the mini-lung to be a universal model system that will allow studying SARS-CoV-2 and any other respiratory virus affecting the alveoli. It is extremely important that the mini-lungs are 100% made up of human cells and do not contain supporting cells that could distort the results of experiments.
The researchers tested the organoid by infecting it with the SARS-CoV-2 coronavirus. They observed the activity of genes and chemical signals that are produced by lung cells after infection.
By changing the genome of the virus, the group gave it the ability to glow. This glow helped the researchers determine where the virus lingers when it comes into contact with lung tissue. It also turned out that when infected with coronavirus, an inflammatory reaction mediated by interferons is triggered in organoids.
The researchers witnessed a cytokine storm in response to the virus. Previously, it was thought that such a reaction happens due to a large influx of immune cells, but experiments on mini-lungs have shown that changes also occur at the level of lung stem cells.
On mini-lungs, the group observed how cells produce interferons and die as a result of self–destruction - the same processes were noted in samples obtained from patients with Covid-19. The signal of cellular suicide was sometimes triggered in uninfected neighboring lung cells. The researchers also compared gene activity patterns in mini-lungs and samples from six patients with severe Covid-19 and found striking similarities.
In another series of experiments, mini-lungs treated with low doses of interferons before infection were able to slow down the replication of the virus. And suppression of interferon activity before infection led to increased replication of the virus.
Tata and his group plan to collaborate with both academic and industrial partners to eventually try to grow a full-fledged lung for transplantation. In addition, the mini-lungs will be used to better understand a new strain of SARS-CoV-2 called D614G, which is now the dominant version of the virus.
Article by H.Katsura et al. Human Lung Alveolospheres Provide Insights Into SARS-Cov-2 Mediated Interferon Responses and Pneumocyte Dysfunction published in the journal Cell Stem Cell.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Duke Today: Lab-grown mini-lungs mimic the real thing - right down to covid infection.