Researchers at Rockefeller University have developed a cell culture platform in which to grow ‘lung buds’ from human embryonic stem cells. The tiny structures are similar to the lung buds that form during fetal development, and they contain tiny airways and alveoli. The researchers create the structures in a bio-reactor style device that is furnished with microfluidic chips in which the lung buds grow. The team developed a cocktail of growth factors that can stimulate the embryonic cells to differentiate into the lung buds, and they hope to use the system to test how respiratory infections behave and to discover new treatments. The lung buds are genetically identical, reducing the biological variability inherent to such testing, and allow the researchers to perform experiments without using experimental animals.
Researchers are getting better at creating ‘mini-organs’ in the lab. Such organoids are enormously useful in learning the mechanisms underlying disease and testing new treatments. The recent COVID-19 pandemic has spurred scientists to develop a better understanding of respiratory disease – after all, some of the most contagious diseases are spread through the air, so understanding how they infect and develop in lung tissue would go a long way towards helping us to be better prepared for the next pandemic.
The new lung buds developed by these researchers can be created in their thousands, allowing the researchers to study thousands of individual SARS-CoV-2 infections at the same time, for instance. “These lungs are basically clones,” said Ali Brivanlou, a researcher involved in the project. “They have the exact same DNA signature. That way we don’t have to worry about one patient responding differently from another. Quantification allows us to keep the genetic information constant and measure the key variable — the virus.”
The new technology involves seeding embryonic stem cells in microfluidic chips and then exposing them to a cocktail of growth factors to stimulate them to turn into lung tissue. The tiny structures closely match adult lung tissues, with small airways and alveoli. The technology has already yielded some interesting phenomena about SARS-CoV-2, revealing that alveoli are more susceptible to infection than airway cells, and the researchers also identified a signaling pathway that makes lung tissue more susceptible to infection. Blocking this pathway may represent a new therapeutic target.
“The platform will also allow us to respond to the next pandemic with much more speed and precision,” said Brivanlou. “We can quickly capitalize on this platform to make a virus visible and develop therapies much faster than we did for COVID. It can be used to screen for drugs, compounds, vaccines, monoclonal antibodies, and more directly in human tissue. This technology is ready to confront all kinds of threats that may hit us in the future.”
Study in journal Stem Cell Reports: Organotypic human lung bud microarrays identify BMP-dependent SARS-CoV-2 infection in lung cells