A team of researchers have developed a mini-lung in the lab made of thousands of human lung stem cells. This breakthrough is now being used to understand what SARS-CoV-2 and other airborne pathogens do to our lung cells. The development is reported in the journal Cell Stem Cell.
The team used alveolar epithelial type-2 cells (AT2s), a type of lung stem cell that repairs the deepest portions of our respiratory system. This is where the exchange of oxygen and carbon dioxide from our bloodstream takes place.
In the lab, these cells can be made to multiply into millions of cells, recreating a portion of the human lung. Researchers can then study at a molecular level the behavior of these cells when infected with the SARS-CoV-2 virus. This could provide important insights into treating patients with Covid-19.
“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,” lead author Purushothama Rao Tata from Duke University said in a statement.
The stem cells are grown in a chemically pure culture, so no contamination from things other than human cells could mess with the results. “This is a major breakthrough for the field because we were using cells that didn’t have purified cultures,” said co-author Ralph Baric, a distinguished professor of epidemiology, microbiology and immunology at the University of North Carolina. “This is incredibly elegant work to figure out how to purify and grow AT2 cells in culture in pure form."
The team confirmed that when lung cells are infected with SARS-CoV-2, the virus homes in on the ACE2 cell surface receptor. The lung cells then release a storm of immune molecules in response to the virus. The release of interferons — signaling proteins that warn other cells of a virus — also appears to lead some cells to enter a self-destruct mode to stop the spread of the virus. Unfortunately, these signals also triggered uninfected neighboring cells. The researchers compared the genetic activity of these cells with actual cells in humans and found a “striking similarity”.
“We’ve only been able to see this from autopsies until now,” Tata said. “Now we have a way to figure out how to energize the cells to fight against this deadly virus.” By reducing or increasing the level of interferon activity, the team could also increase or reduce viral replication, respectively.
The Covid-19 pandemic has passed 46.6 million cases worldwide with over 9 million in the United States alone. Over 1.2 million people have died because of the disease, with over 231,000 casualties in the US.