Article by Dr. Francis Collins, NIH Director’s Blog

Researchers have become skilled at growing an array of miniature human organs in the lab. Such lab-grown “organoids” have been put to work to better understand diabetes, fatty liver disease, color vision, and much more. Now, NIH-funded researchers have applied this remarkable lab tool to produce mini-lungs to study SARS-CoV-2, the coronavirus that causes COVID-19.

The intriguing bubble-like structures (red/clear) in the mini-lung pictured above represent developing alveoli, the tiny air sacs in our lungs, where COVID-19 infections often begin. In this organoid, the air sacs consist of many thousands of cells, all of which arose from a single adult stem cell isolated from tissues found deep within healthy human lungs. When carefully nurtured in lab dishes, those so-called alveolar epithelial type-2 cells (AT2s) begin to multiply. As they grow, they spontaneously assemble into structures that closely resemble alveoli.

A team led by Purushothama Rao Tata, Duke University School of Medicine, Durham, NC, developed these mini-lungs in a quest to understand how adult stem cells help to regenerate damaged tissue in the deepest recesses of the lungs, where SARS-CoV-2 attacks. In earlier studies, the researchers had shown it was possible for these cells to produce miniature alveoli. But there was a problem: the “soup” they used to nurture the growing cells included ingredients that weren’t well defined, making it hard to characterize the experiments fully.

In the study, now reported in Cell Stem Cell, the researchers found a way to simplify and define that brew. For the first time, they could produce mini-lungs consisting only of human lung cells. By growing them in large numbers in the lab, they can now learn more about SARS-CoV-2 infection and look for new ways to prevent or treat it.

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