When surgeons removed a 33-year-old woman’s right lung as part of her cancer treatment in 1995, they expected a dramatic and permanent reduction in her breathing power. But that’s not what happened. Instead, her remaining lung pulled off a trick that scientists had long thought impossible in humans: it grew new tissue, and lots of it. Over the next 15 years, her left lung compensated for the loss of its partner by nearly doubling in volume and growing millions of new air sacs, called alveoli1.
“Until then, the prevailing view was that lungs are not really regenerative,” says Purushothama Rao Tata, a biologist at Duke University School of Medicine in Durham, North Carolina. “But in my view, lungs are not really different from liver,” he says. “Lungs have tremendous regenerative capacity.”
Nature Outlook: Lung health
Over the past decade or so, researchers have started exploring the regenerative abilities of the lungs in earnest. The findings are changing how scientists see the organ. It is becoming clear that lungs, although quiescent when undisturbed, are able to react and respond to injury or infection, thanks to specialized cells that have a surprising ability to morph from one type to another. Faults in this process are also emerging as key mechanisms behind lung diseases, such as chronic obstructive pulmonary disease (COPD), raising the intriguing possibility that this currently incurable condition could be slowed, stopped or even reversed.
Such treatments are sorely needed. “COPD is the third leading cause of death in the world,” says Ed Morrisey, a biologist who studies lung development and regeneration at the University of Pennsylvania in Philadelphia. “And yet we don’t have any really good therapy.” For other diseases such as idiopathic pulmonary fibrosis (IPF) — a fatal condition in which the lungs become progressively scarred and stiff — the outlook is similarly bleak. Even with a lung transplant, respite from IPF is usually only temporary because recipients often don’t survive for longer than about five years. Researchers hope that the hitherto overlooked ability of the lungs to rebuild themselves might hold answers.
Hidden potential
One reason that the adult human lung’s ability to regenerate flew under the radar for so long is because it can partly compensate for lost tissue by drawing on physiological spare capacity. Age is another. Young mice and rats, for example, rapidly grow extra tissue when one lung is removed, but this ability declines as the animals get older. Young children can regrow some lung tissue. This is possibly related to human lung development continuing after birth and into the teenage years. But, as with rodents, this ability seems to diminish with age. What’s more, surgery to remove lung tissue is usually performed on older adults. Lung recovery is not followed up long-term, meaning signs of regeneration would be missed.
Yet, it has long been clear that the lung must have some repair capacity — after all, people routinely recover from lung injury caused by viral infections, such as influenza. By the early 2000s, researchers were developing the tools to explore lung regeneration in detail. Pioneering work by developmental biologist Brigid Hogan and her team at Duke in 2009, for example, definitively established2 that basal cells in the lung airways act as stem cells, which can generate specialized cell types. Reports of lung regrowth in humans (including in the 33-year-old woman with cancer) followed. And around the same time, research on the mouse lung showed how stem cells contribute to regeneration.
Thanks to innovations, such as ‘omics’ technologies for studying gene activity in space and time; advanced cell-culture techniques, including keeping human lung slices alive; and 3D mini-lung structures grown from stem cells, called organoids, discoveries have multiplied at pace. Cell atlases3 of healthy and diseased lungs have identified about 70 predicted cell types and linked specific types to genes involved in COPD and fibrosis.
Human lung organoid.Credit: Ziqi Dong/ https://doi.org/10.1016/j.stem.2025.09.007
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