Genetically Identical Lung Buds Could Accelerate the Study of Respiratory Diseases

Data from patient lung tissues greatly varies from person to person, obscuring the basic mechanisms of how, exactly, SARS-Co-V2 first infects lung cells. It’s also an after-the-fact analysis — as if we’re trying to map the route the virus took three states back.

Turning down the noise of variability by studying genetically identical tissues from the first moment of infection could light up the route the pathogen takes. Which cells are infected, and when? What is the level of infection, and how does it differ depending on cell type? How does it change in different conditions?

And what if it were possible to track thousands of these infections at once? It might revolutionize our understanding of both infections and the drug treatments used to combat them.

That’s the hope for new advanced tech capable of growing mini organs on microchips. 

The labs of Rockefeller’s Ali Brivanlou and Charles M. Rice collaborated to refine a cell culture technology platform that grows genetically identical lung buds — the embryonic structures that give rise to our breathing organs — from human embryonic stem cells (hESCs). Their findings were recently published in Stem Cell Reports.

The result is unlimited, fast, and scalable access to lung tissue that has the key hallmarks of human lung development and can be used to track lung infections and identify candidate therapeutics.

Embryonic stem cells are the Ur-cells of the human body. They can infinitely divide to create more stem cells or to differentiate into any other tissue. Brivanlou’s Laboratory of Synthetic Biology has long explored their potential.

Brivanlou joined forces with Rockefeller colleague Charles M. Rice during the COVID pandemic: his lab had the microchip technology to grow lung buds, and Rice’s lab had the necessary biosafety clearance required to infect them with SARS-Co-V2 and study the outcome.

Since then, they’ve used the platform to understand how SARS-Co-V2 infects different lung cells.

The researchers note that the platform can also be used to investigate the mechanisms of influenza, RSV, pulmonary diseases, and lung cancer, among other diseases. Moreover, it can be used to screen for new drugs to treat them.

“The platform will also allow us to respond to the next pandemic with much more speed and precision,” Brivanlou adds. “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.”

Sources:

E.A. Rosado-Olivieri, B. Razooky, J. Le Pen, R. De Santis, D. Barrows, Z. Sabry, H.-H. Hoffmann, J. Park, T.S. Carroll, J.T. Poirier, C.M. Rice, A.H. Brivanlou. Organotypic human lung bud microarrays identify BMP-dependent SARS-CoV-2 infection in lung cells. Stem Cell Reports, 2023; 18 (5): 1107 DOI: 10.1016/j.stemcr.2023.03.015

Rockefeller University. (2023, June 1). Lab-grown mini lungs could accelerate the study of respiratory diseases. ScienceDaily. Retrieved June 5, 2023 from www.sciencedaily.com/releases/2023/06/230601155927.htm
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