Human lungs possess a genuine, if limited, ability to grow new tissue and repair damage. A landmark case published in the New England Journal of Medicine documented new lung growth in an adult woman after she had an entire lung removed, providing the first direct evidence that humans can form new air sacs rather than simply stretching existing ones. But the picture is complicated. This regenerative capacity varies dramatically with age, the type of injury, and underlying health conditions. In chronic diseases like emphysema, the very cells responsible for repair become dysfunctional, which is why damaged lungs so often stay damaged.
The First Proof in a Living Human
For decades, researchers assumed that adult human lungs could not grow new alveoli, the tiny air sacs where oxygen enters the blood. Animal studies had long shown that mice and rats could regrow portions of lung after surgical removal, but whether this applied to people was an open question. That changed with a single patient: a young woman who had her right lung removed (pneumonectomy) due to a rare vascular condition. Over the following fifteen years, serial CT scans of her remaining left lung showed it progressively enlarging and becoming denser with tissue. More telling, specialized MRI scans using hyperpolarized helium gas revealed that the dimensions of her airway structures were consistent with new alveoli forming, not just existing ones inflating larger. The new alveoli were shallower than those in a normal lung, suggesting the growth was real but not a perfect copy of the original architecture.
1PubMed Central. Evidence for adult lung growth in humansThis case was a proof of concept, not proof that all adults can easily regenerate lung tissue. The patient was young, had lost an entire lung (creating enormous mechanical stimulus on the remaining one), and was otherwise healthy. Still, it upended the textbook assumption that adult human lungs were static organs incapable of structural growth.
Why Children Recover Better Than Adults
Children who lose a lobe or an entire lung tend to recover more lung function over time than adults undergoing the same surgery. A systematic review of pulmonary function after lobectomy in children found that human lungs retain compensatory growth capacity across the lifespan, but children were considered to have the stronger ability.
2BMJ. Pulmonary function after lobectomy in children: a systematic review and meta-analysisLong-term follow-up studies after pneumonectomy in children found that the remaining lung’s total capacity eventually reached about 62% of what a person with both lungs would have. Adults who underwent the same surgery reached a similar percentage, but with an important difference: adult patients showed larger residual volumes, meaning more air was getting trapped rather than being used for gas exchange. In children, the compensation appeared to come more from genuine new alveolar tissue rather than simple over-inflation.
3Pharmacology & Therapeutics. The pneumonectomy model of compensatory lung growth: Insights into lung regenerationAge at surgery matters within childhood too. A longitudinal study of children who had a lung lobe removed found that those operated on after age four showed lower vital capacity and more air trapping compared with younger children. Preoperative lung infections and thoracic deformities also worsened outcomes, suggesting that the regenerative window narrows quickly and that pre-existing damage can compromise it.
4PubMed. Longitudinal follow-up of pulmonary function after lobectomy in childhood – factors affecting lung growthThe Cells That Make Repair Possible
Lung repair hinges on a specific population of cells called alveolar type II cells, or AT2 cells. These cells have a day job: they produce surfactant, the slippery substance that keeps air sacs from collapsing. But when the lung is injured, AT2 cells switch roles. They can divide to replenish their own numbers and also transform into alveolar type I cells, the flat, thin cells that form the gas-exchange surface. Because of this dual ability, researchers describe AT2 cells as “facultative stem cells,” meaning they only activate their regenerative function when called upon by injury.
5PubMed Central. Heterogeneous groups of alveolar type II cells in lung homeostasis and repair 6Chinese Medical Journal Pulmonary and Critical Care Medicine. Epithelial stem cells and niches in lung alveolar regeneration and diseases
AT2 cells are not alone. In the airways, basal stem cells serve as another reserve force. These cells sit at the base of the airway lining and can differentiate into multiple cell types to rebuild the epithelial barrier after severe injury.
7PubMed Central. Control of airway basal stem cell-mediated lung repair by TGF-β signalingThere is also a rarer population hiding among the club cells of the distal airways. Roughly 5% of these club-like cells are distinct progenitors that can mobilize after serious alveolar damage, migrating into denuded air sacs and helping rebuild normal barriers. The lung, in other words, maintains multiple overlapping backup systems for repair, each tuned to different scales of injury.
8PubMed Central. Distinct Airway Epithelial Stem Cells Hide among Club Cells but Mobilize to Promote Alveolar RegenerationWhat Triggers the Lung to Grow
Stem cells sitting quietly in lung tissue need signals to wake up. Two of the most important triggers are mechanical stretch and blood vessel signaling.
When a lung or lobe is removed, the remaining tissue is suddenly responsible for all of the body’s gas exchange. Each breath stretches the surviving lung more than it was designed for. This increased mechanical strain acts as a powerful growth signal. Research comparing developing lungs and compensatory lung growth in adults has found that physical stress on the tissue, the vasculature, and the chest wall can re-initiate growth in mature lungs, but only when the loss of functioning lung exceeds a critical threshold that overwhelms the organ’s built-in reserve capacity.
9PubMed Central. Comparative analysis of the mechanical signals in lung development and compensatory growth 10PubMed Central. What do we know about mechanical strain in lung alveoli?
Blood vessels play a surprisingly active role too, going beyond just delivering oxygen. After pneumonectomy in animal models, the capillary cells lining lung blood vessels start producing growth factors that directly tell epithelial progenitor cells to multiply and form new alveoli. Specifically, these capillary cells release an enzyme called MMP14 that unmasks growth signals normally kept hidden, kick-starting the regenerative process.
11PubMed Central. Endothelial-Derived Inductive Angiocrine Signals Initiate and Sustain Regenerative Lung AlveolarizationThe extracellular matrix, the scaffold of proteins and fibers that gives lung tissue its shape, also plays a regulatory role. It is not just passive architecture. The matrix sends biochemical and physical cues to cells, influencing whether they grow, repair, or sit idle. When the matrix becomes disorganized, as it does in fibrotic lung disease, it can actively drive cells toward abnormal behavior rather than healthy repair.
12PubMed Central. Extracellular matrix in lung development, homeostasis and diseaseWhat Animal Studies Have Shown
Much of what we know about lung regeneration comes from mice, rats, and more exotic species. In mice, removing the left lung (which accounts for about 40% of total alveoli) triggers the remaining right lung to grow new alveoli rapidly. One study counted the alveoli precisely and found that by 20 days after surgery, the right lung had regenerated roughly half the alveoli that had been removed. Remarkably, about three-quarters of that new growth happened within the first six days.
13European Respiratory Journal. Neoalveolarisation contributes to compensatory lung growth following pneumonectomy in miceEven more striking are axolotl salamanders, which are famous for regrowing entire limbs. Their lungs regenerate differently from their legs: instead of forming a concentrated bud of new growth, lung injury triggers organ-wide proliferation. Cells throughout the entire injured lung ramp up their division, and within about 56 days the lung recovers its mass and shape.
14PubMed. Lung injury in axolotl salamanders induces an organ-wide proliferation responseThe gap between axolotls and humans is enormous, of course. But studying these different strategies of regeneration helps researchers identify which molecular pathways matter most and which ones might be pharmacologically enhanced in people.
When the Repair System Breaks Down
The regenerative machinery described above works best in otherwise healthy lungs responding to a clean surgical loss. Chronic lung diseases are a different story. In COPD and emphysema, the progenitor cells themselves become defective. The persistent inflammation, ongoing tissue destruction, and signals from the damaged micro-environment impair the ability of epithelial stem cells to proliferate and differentiate normally.
15PubMed. The impact of the immune system on lung injury and regeneration in COPDResearch into the molecular details has identified specific deficiencies. The support cells surrounding alveoli in emphysema lungs produce fewer of the growth factors that AT2 cells need to carry out repair.
16PubMed. Abnormalities in reparative function of lung-derived mesenchymal stromal cells in emphysemaEven the energy metabolism of AT2 cells can go wrong. Recent work has found that a key energy-transport protein is reduced in AT2 cells from COPD lungs, which impairs the cells’ ability to produce ATP and makes them vulnerable to a form of cell death called ferroptosis. Without enough energy and with increased susceptibility to dying, these progenitor cells lose their self-renewal capacity.
17PubMed Central. Adenine nucleotide translocase 2 (ANT2) deficiency reprograms ferroptosis in alveolar progenitor cells to promote emphysemaFibrosis presents another barrier. When the extracellular matrix becomes scarred and stiff, as it does in idiopathic pulmonary fibrosis, the altered scaffold itself promotes further scarring. Normal lung cells seeded onto fibrotic scaffolds in laboratory experiments differentiate into the stiff, contractile cells that produce more scar tissue, even without the usual biochemical signals for fibrosis. The matrix essentially corrupts the cells that land on it.
18iScience. Do Lungs Grow Back? The Reality of Lung RepairSmoking and Viral Infections Sabotage Repair
Cigarette smoke has a paradoxical effect on lung stem cells. Exposure to smoke triggers airway basal stem cells to proliferate as part of a repair response, which sounds beneficial. But when a viral infection like SARS-CoV-2 enters the picture, the expected stem cell mobilization fails. In laboratory airway cultures, cigarette smoke exposure alone increased the number of basal stem cells, yet SARS-CoV-2 infection, whether combined with smoke or not, blocked the increase in stem cells needed for proper repair. The virus essentially inhibits the airway’s ability to heal itself.
19Cell Stem Cell. Direct Exposure to SARS-CoV-2 and Cigarette Smoke Increases Infection Severity and Alters the Stem Cell-Derived Airway Repair ResponsePost-COVID lung damage has drawn particular attention to how viral injuries become chronic. A 2025 study in Science found that immune cells called macrophages, which normally help clean up after infection, rely on specialized compartments called peroxisomes to guide healthy alveolar regeneration. When peroxisome function is impaired, macrophages become overactivated and release inflammatory signals that cause epithelial progenitor cells to become dysplastic, stuck in an abnormal state rather than completing their transition into functional alveolar cells. This contributes to the lingering lung scarring and breathing difficulties seen in long COVID. Encouragingly, the same study found that pharmacologically boosting peroxisome production reduced both acute symptoms and post-acute lung damage in animal models.
20PubMed Central. Macrophage peroxisomes guide alveolar regeneration and limit SARS-CoV-2 tissue sequelaeThe Promise and Frustration of Retinoic Acid
One of the most tantalizing findings in lung regeneration research involves retinoic acid, a derivative of vitamin A. In the late 1990s, researchers gave retinoic acid to rats whose lungs had been damaged with an enzyme to mimic emphysema. The results were dramatic: new alveoli formed, and both alveolar number and gas-exchange surface area were restored essentially to normal.
21Drug Discovery Today: Disease Mechanisms. Retinoids and pulmonary alveolar regeneration: Rationale and therapeutic challengesThe working theory was that retinoic acid reactivates developmental gene programs that built the alveoli in the first place. During normal lung development, retinoic acid plays a critical role in alveolar formation, and giving it to adults may re-awaken those same signaling cascades.
22PubMed Central. Retinoic acid in alveolar development, maintenance and regenerationThese results generated real excitement, but translating them to humans has proved difficult. Human trials with retinoids for emphysema have been disappointing so far, with no clear clinical benefit in the studies completed to date. The reasons likely involve the differences between a clean experimental injury in a young rat and the years of accumulated damage, inflammation, and matrix remodeling present in a person with established emphysema. The concept remains scientifically interesting, but nobody should interpret it as a current treatment option.
Bioengineered Lungs and Organoids
If the body’s own repair systems fall short, could we build a lung from scratch? That is the ambition behind lung bioengineering. The approach involves taking a donor lung, stripping away all its cells with detergent solutions to leave behind a bare scaffold of extracellular matrix, and then reseeding that scaffold with a patient’s own cells. The scaffold retains the organ’s three-dimensional architecture, the branching airways and delicate alveolar chambers, providing a template for new cells to populate.
23PubMed Central. Can stem cells be used to generate new lungs? Ex vivo lung bioengineering with decellularized whole lung scaffoldsProgress is real but incremental. In one experiment, researchers seeded a decellularized rat lung scaffold with fat-derived stem cells and endothelial cells. The stem cells differentiated into pericytes, which are support cells that stabilize blood vessels, reducing vascular leakiness and bleeding when the bioengineered lung was transplanted into a rat. The transplanted lung survived for up to three hours after the ventilator was disconnected.
24Scientific Reports. Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cellsThree hours is obviously nowhere near clinical utility. The lung is one of the most complex organs in the body, with over 40 distinct cell types arranged in an incredibly thin barrier between air and blood. Recreating that in a bioengineered scaffold remains a major challenge. But the field continues to advance in its techniques for decellularization, cell seeding, and maturation of tissue.
25PubMed Central. Lung bioengineering: advances and challenges in lung decellularization and recellularizationOn a smaller scale, lung organoids have become a powerful research tool. These are tiny, self-organizing clusters of lung cells grown in a dish that mimic the architecture of airways or alveoli. Organoids derived from adult stem cells allow researchers to study lung regeneration, infection responses, and even tumor development in conditions that are far more realistic than traditional flat cell cultures. They also expand efficiently from small amounts of donor tissue, making the research more practical and ethical.
26PubMed Central. Distal lung organoids derived from adult stem cells as novel tools in deciphering mechanisms of lung regeneration, infection, and cancerMesenchymal Stem Cell Therapy
Among the therapeutic strategies closest to clinical application are mesenchymal stem cells, which can be harvested from bone marrow, fat tissue, or umbilical cord blood. These cells do not typically become lung cells themselves. Instead, they act as biological pharmacies, releasing anti-inflammatory molecules, dampening harmful immune responses, and promoting tissue repair in their surroundings.
27Cell Death Discovery. Mesenchymal stem cells for lung diseases: focus on immunomodulatory actionIn preclinical models, mesenchymal stem cells and the tiny vesicles they release have been shown to reduce inflammation, limit the infiltration of damaging immune cells into lung tissue, and improve the lungs’ ability to clear fluid from the air spaces.
28PubMed. Mesenchymal stem cell therapy against ischemia-reperfusion injury in lung transplantationOne especially promising application involves ex-vivo lung perfusion, a technique where donated lungs that were initially deemed too damaged for transplant are kept alive outside the body on a perfusion machine. Researchers are exploring whether treating these lungs with mesenchymal stem cells during perfusion can recondition the tissue, regenerate damaged areas, and modulate the recipient’s immune response to reduce rejection. If this works at scale, it could expand the pool of usable donor lungs considerably.
Nutrition, Calorie Restriction, and Lung Stem Cells
Nutrition influences lung repair in ways that might surprise you. In mouse studies, calorie restriction increased the number and colony-forming ability of lung stem cells in both young and old animals. Aging normally causes a decline in tracheal basal stem cells and reduces their regenerative efficiency, but calorie-restricted mice showed improvements in both measures regardless of age.
29PubMed. Calorie restriction enhances adult mouse lung stem cells function and reverses several ageing-induced changesIn a striking experimental model, calorie restriction in mice actually caused alveolar loss, mimicking a form of emphysema. But when those mice were then allowed to eat freely again, their lungs began regenerating alveoli. Gene expression patterns associated with building new alveolar walls appeared within just three hours of refeeding, and DNA synthesis ramped up shortly afterward.
30PubMed. Rapid onset of gene expression in lung, supportive of formation of alveolar septa, induced by refeeding mice after calorie restrictionThese findings are far from actionable health advice for people with lung disease. The calorie restriction in these studies was severe and experimentally controlled. But they reveal something fundamental about lung biology: the organ retains dormant regenerative programs that can be switched on under the right metabolic conditions, even in older animals. Understanding those switches is a major goal for researchers trying to develop drugs that could coax damaged human lungs into rebuilding themselves.