Lab-Grown Micro Lungs Could Boost Understanding of Lung Infections, Respiratory Conditions

Scientists were able to come up with a novel cell culture technology that produces micro lung clones on microchips from stem cells. This offers a new way to study respiratory conditions and lung infections, such as SARS-CoV-2.

Lab-Grown Micro Lungs

According to Science Daily, labs of Charles M. Rice and Ali Brivanlou of Rockefeller University collaborated with each other to refine a platform for cell culture technology that grows lung buds that are genetically identical. They did so out of human embryonic stem cells (hESCs).

When these are stationed on a microchip array and carefully given some custom cocktail of molecule signals, these hESCs quickly self-organize into micro lungs that have the complexity of full tissues. Such findings were detailed further in the Stem Cell Reports.

Ali Brivanlou explains that the micro lungs are essentially clones that hold identical DNA structures. Brivanloud adds that this means that they need not worry about one patient having a different response compared to another. Quantification enables the genetic data to remain constant. It also further enables the key variable, the virus, to be gauged.

Culturing these buds can be done by the thousands. This enables the analysis of lung tissue infections with high throughput and without other disruptive variables. It results in scalable, fast, and unlimited access to lung tissue, which holds essential hallmarks of the development of human lungs. This could be used to monitor lung infections and look for potential treatments.

Ali Brivanlou cooperated with Charles M. Rice, a colleague from Rockefeller University, while the COVID pandemic was ongoing. Brivanlou's lab had the microchip technology for nurturing lung buds, while Rice's lab had the required biosafety clearance for infecting such buds with the coronavirus and examining their outcomes, SciTechDaily reports.

Back in 2021, stem cell biologist Edwin Rosaldo-Olivieri and postdoc Brandon Razooky, first authors who were from Brivanlou and Rice's laboratories, respectively, started coaxing the cells to organize into forms that were more specialized. Stem cells do not just self-organize; they require confined space and stimuli for changes to take place.

After roughly two weeks, the lung cells formed buds that had molecular profiles that closely aligned with the ones observed in the earliest phases of fetal development. This included alveoli and airway formation, which are both structures that are known to get damaged among several individuals dealing with severe COVID-19.

Knowing More About Lung Infections and Respiratory Conditions

The researchers have been using the platform to learn more about how the virus infects various lung cells.

Alveoli, specifically, are small sacs situated by the end of lung branches that handle gas exchanges performed at each breath. As the researchers examined alveoli clone cells en masse, they found that these cells had higher susceptibility to the coronavirus compared to airway cells.

The researchers were also able to come up with a "winning combination" of protein signals for making robust lung bud batches. This comprised a combination of keratinocyte growth factor (KGF) and bone morphogenetic protein 4 (BMP4). Both impact cell growth and differentiation. They also discovered that blocking the pathway of the BMP decreased the vulnerability of cells.

The authors note that the novel platform could be used to examine mechanisms behind lung cancer, pulmonary conditions, RSV, and influenza, among other conditions. Moreover, it can also be used for screening new drug treatments.

They may even go beyond the lungs, as the pancreas, kidneys, and liver are all potential next targets.

Brivanlou notes that the platform would enable them to respond more quickly and precisely to the next pandemic. He adds that this platform can be capitalized on for making the virus visible and coming up with treatments faster compared to what was done for COVID-19. As it could be used to screen for vaccines, drugs, monoclonal antibodies, and compounds, such technology could help in confronting various threats that humanity could face in the future.

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