Researchers Mend Harmed Contributor Lungs, Offering Plan to Waitlisted Patients
Researchers Mend Harmed Contributor Lungs: From 2019's Pig Bioreactor to Today's CRISPR‑Gene‑Edited Revolution
Let's be honest: lungs are the divas of the organ world. They're delicate, finicky, and exposed to the outside environment through every breath we take. Unlike a kidney, which can be flushed, packed in ice, and shipped across the country with relatively little fuss, lungs are easily damaged—by gastric aspiration, by inflammation, by the very act of dying itself. That's why, for decades, transplant surgeons have faced a maddening reality: roughly 80% of donor lungs are deemed too damaged to use. Patients languish on waiting lists, sometimes for years, knowing that a perfectly good set of lungs might be out there somewhere—they just can't be fixed in time. Back in 2019, when this article was first published, a team of researchers led by Dr. Matthew Bacchetta at Columbia University did something that sounded almost crazy: they hooked damaged pig lungs up to a living pig's bloodstream and let the donor's own body do the healing. The lungs recovered over three days and worked more than 30 times better than control lungs. It was a brilliant, audacious proof of concept—and it cracked open a door that has since been kicked wide open.
Fast forward to 2026, and the landscape of lung transplantation has been utterly transformed. The "bioreactor" approach that Bacchetta pioneered—using a living recipient's body to heal a damaged organ—has evolved into a multi‑pronged scientific enterprise encompassing AI‑driven ex vivo lung perfusion (EVLP), CRISPR gene editing, stem cell therapies, xenotransplantation, and even a total artificial lung that can keep a patient alive for 48 hours with no lungs at all. The global shortage of transplantable lungs remains acute—more than 8,000 people are on the waiting list in the UK alone, and waitlist mortality hovers around 30% in many regions—but the tools to address that shortage are finally coming online. As Bacchetta said back in 2019, "There's such a deficiency of contributor organs. We were … hunting down an approach to stretch out the capacity to give life‑sparing treatment to patients." That hunt is now yielding results—and they're saving lives every day.
"We attach[ed] the organ to a potential beneficiary, who really gives the physiologic milieu that you have to recuperate, to give the vitality substrate and the component for freeing the assortment of waste."
The 2019 Breakthrough: Using a Living Body as a Bioreactor
The original study, published in Nature Communications in May 2019, was a masterclass in creative problem‑solving. Bacchetta and his team induced lung damage by pouring digestive acid into one lung of a sedated pig, simulating the gastric aspiration that frequently renders human donor lungs unusable. After six hours of acid exposure, the lungs were removed and placed in a sterile organ chamber, where they were hooked up to a ventilator. But instead of relying on a mechanical perfusion system alone, the researchers connected the damaged lungs to the major blood vessels of a live "recipient" pig. The recipient's oxygen‑rich blood was pumped into the disembodied donor lungs, and the donor's deoxygenated blood was returned to the recipient's body for cleansing. In effect, the recipient pig served as a living bioreactor—providing the metabolic support, waste removal, and physiological milieu that the damaged lungs needed to heal.
The results were astonishing. Over the course of three days, the researchers flushed the gastric acids out of the lungs, treated them with surfactant (a substance that helps lungs expand and contract), and let the recipient's body do the rest. The recovered lungs worked more than 30 times better than control lungs. "I cautioned my lab, I stated, 'We will do this, I know it's sort of insane, simply don't be amazed if the entire thing explodes not long after we begin,'" Bacchetta recalled. It didn't. The lungs healed. The recipient pig survived. And a new paradigm for organ recovery was born.
The implications were profound. If the same approach could be applied to human donor lungs—connecting them to a potential recipient's bloodstream to give them time to heal—the number of usable organs could expand dramatically. Bacchetta and his colleagues envisioned using a "recipient bioreactor" to recover severely damaged human lungs, expanding the donor pool and saving lives. But the approach also raised practical and ethical questions. Could it be scaled? Could the recipient's body be protected from the inflammatory cascade that often accompanies organ injury? And could the same principle be applied to other organs—hearts, livers, kidneys? The 2019 study didn't answer all these questions, but it pointed the way forward. And in the years since, researchers around the world have been racing to build on Bacchetta's insight—using a combination of ex vivo perfusion, gene therapy, and advanced engineering to mend damaged lungs before they ever touch a recipient's bloodstream.
The EVLP Revolution: From Assessment to Active Repair
If Bacchetta's bioreactor was the radical, outside‑the‑box idea, ex vivo lung perfusion (EVLP) is the workhorse that has made lung repair a clinical reality. EVLP is a technique that keeps donor lungs alive outside the body by perfusing them with a nutrient‑rich solution and ventilating them with oxygen. Originally developed as a tool to assess marginal lungs—to see if they could oxygenate blood well enough to be transplanted—EVLP has evolved into a platform for active therapeutic intervention. "Ex‑vivo lung perfusion has emerged as a breakthrough in lung transplantation, enabling both functional assessment of donor lungs and therapeutic interventions to rehabilitate marginal grafts," notes a 2025 protocol published in JoVE[reference:0]. "As such, EVLP provides the unique opportunity to rehabilitate damaged (marginal) lungs and reduce the risk of primary graft dysfunction (PGD), a major complication impairing both early and long‑term outcomes after lung transplantation."
The numbers speak for themselves. A 2025 North American expert consensus, published in the Journal of Thoracic Disease, affirmed that EVLP has become an essential tool for expanding the donor pool. "Ex vivo lung perfusion (EVLP) has resulted in a significant increase in the use of extended‑criteria donor lungs without negatively impacting survival outcomes," the consensus noted[reference:1]. Remote, centralized EVLP (rc‑EVLP) has been particularly transformative. A 2025 study of 82 extended‑criteria donor lungs assessed by rc‑EVLP found that 56% were ultimately transplanted, with a primary graft dysfunction (PGD) rate of just 17% and 1‑year survival of 93%[reference:2]. Even lungs from donation after circulatory death (DCD)—historically considered high‑risk—achieved 100% 1‑year survival when assessed by rc‑EVLP. "Remote, centralized EVLP increases the use of extended‑criteria donor lungs in a real‑world setting and is associated with excellent outcomes," the authors concluded[reference:3].
But EVLP is not just about assessment. It's increasingly about active repair. A 2025 study published in Frontiers in Physiology introduced a computational physiological model (CPM) that optimizes ventilation and perfusion settings for each individual lung, reducing ventilator‑induced injury and extending the safe duration of EVLP[reference:4]. Another 2025 study demonstrated the feasibility of preserving bronchial artery circulation during EVLP—a technical advance that protects the airways from ischemic damage and could improve long‑term graft function[reference:5]. And perhaps most remarkably, researchers have shown that transient, controlled heat stress—"thermal preconditioning" at 41.5°C for 30 minutes—induces a protective heat shock response in damaged lungs, reducing edema, improving compliance, and lowering biomarkers of endothelial injury[reference:6]. "This reproducible, scalable protocol is adaptable to larger animal or human EVLP systems," the authors note, "providing a practical translational platform for studying non‑pharmacological interventions aimed at improving transplant outcomes."
The clinical trial landscape has been more mixed. A 2025 multicenter randomized trial tested regadenoson, an adenosine receptor agonist, as an adjunct to EVLP for marginal lungs. The results were disappointing: there was no significant increase in the use of marginal lungs or a decrease in ischemic reperfusion injury compared to placebo[reference:7]. But the trial also revealed an important insight: the placebo group had a higher‑than‑expected use rate of 75%, making it difficult for the treatment group to show a benefit. The lesson is that EVLP alone—even without pharmacologic additives—is already highly effective at rehabilitating marginal lungs. The baseline has shifted, and the bar for new interventions is higher than ever.
"EVLP offers expansion of the donor pool by testing lungs of marginal quality and facilitating a logistical bridging platform for lungs of standard quality. When their function stabilizes or improves during EVLP, post‑transplant outcomes are comparable to standard quality lungs."
The Gene Editing Frontier: CRISPR Comes to the Donor Lung
If EVLP is the platform, gene editing is the precision tool that could transform lung transplantation from a desperate last resort into a routine, predictable procedure. The logic is compelling: instead of relying on the donor lung's native biology—which may be damaged, inflamed, or immunologically hostile—why not use the EVLP window to genetically modify the organ, making it more resilient to ischemia‑reperfusion injury and less likely to provoke rejection? This is no longer science fiction. In 2024, a landmark study published in Human Gene Therapy introduced a novel platform for testing CRISPR‑Cas genome editing in human lungs ex vivo, effectively simulating preimplantation genetic engineering of donor organs[reference:8]. The researchers identified gene regulatory elements whose disruption via Cas nucleases led to the upregulation of interleukin‑10 (IL‑10), a powerful immunomodulatory cytokine. They then combined this approach with adenoviral vector‑mediated IL‑10 delivery to create favorable kinetics for early graft immunomodulation. "Our findings lay the groundwork for a first‑in‑human‑organ study to overcome the current translational barriers of genome‑targeting therapeutics," the authors concluded[reference:9].
The LifeLUNG project, funded by the European Union's Marie Skłodowska‑Curie Actions programme, is taking this concept to the next level. Launched in November 2025, LifeLUNG aims to "precondition donor lungs before transplantation with a dual approach that combines ex vivo lung perfusion and gene therapy"[reference:10]. The project uses advanced machine learning and deep sequencing to identify key immune and gene targets of reperfusion injury, then develops advanced delivery vehicles—adeno‑associated viral vectors, virus‑like particles, and lipid nanoparticles—to ensure precise, graft‑specific genetic modulation. "The LifeLUNG initiative unites the critical building blocks available in Europe to advance towards a novel paradigm for lung transplantation," the project description states[reference:11]. "By utilizing biobanks of lung biopsies from both clinical LTx cases and established animal models … LifeLUNG will apply advanced machine learning and AI‑driven deep sequencing to identify key immune factors and gene targets."
Stem cell therapies are also entering the fray. At Lund University in Sweden, researchers are developing CRISPR‑engineered mesenchymal stem/stromal cells (MSCs) to promote immune tolerance and reduce rejection risk in lung transplantation. "Mesenchymal stem/stromal cell (MSC) based therapies have the potential to ameliorate injured donor lungs and to improve the results of transplantation," the project description notes[reference:12]. The team plans to optimize MSCs to express genes that make the cells immunologically tolerant and protect them from ischemia‑reperfusion injury, then test the modified cells in porcine and human lung models. "This project aims to find novel approaches to increase the number of available donor lungs, to decrease the rate of PGD and to enhance the survival and quality of life of the recipients"[reference:13].
These gene‑editing approaches are not yet in clinical use, but the trajectory is clear. Within the next five to ten years, it may become standard practice to place a marginal donor lung on EVLP, infuse it with a tailored gene therapy vector, and "dial in" the organ's immune profile before it ever touches the recipient. The implications for transplant outcomes—and for the donor organ shortage—are profound.
The Xenotransplantation Breakthrough: Gene‑Edited Pig Lungs in Humans
While researchers work to expand the pool of human donor lungs, another audacious strategy is gaining traction: using gene‑edited pig lungs as a substitute. Xenotransplantation—the transplantation of organs from one species to another—has been a holy grail of transplant medicine for decades, but immunological barriers have repeatedly thwarted progress. That changed dramatically in 2025. In a landmark study published in Nature Medicine, a team of Chinese researchers led by Dr. Jianxing He performed the first successful pig‑to‑human lung xenotransplantation using a six‑gene‑edited Bama Xiang pig[reference:14]. The pig's genome was modified using CRISPR‑Cas9 technology: three pig genes known to provoke strong immune rejection were deleted, and three human genes were inserted to modulate blood clotting and complement activation pathways. The edited lung was transplanted into a brain‑dead human recipient, where it remained viable and functioning for nine days.
"This is the first time a lung transplant of this kind has been performed," the researchers reported. "The organ, which underwent six genetic modifications to make it more compatible with humans, remained viable and functioning for nine days"[reference:15]. The procedure was a critical proof of concept, demonstrating that gene‑edited pig lungs can avoid hyperacute rejection—the catastrophic immune response that has doomed previous xenotransplantation attempts. At the 2025 International Xenotransplantation Association (IXA) congress, researchers reported that an 11‑gene‑edited pig lung, combined with donor macrophage depletion, achieved a record 33‑day survival in a preclinical model, surpassing the previous 31‑day record[reference:16].
The implications are staggering. The global shortage of human donor organs is not a temporary mismatch between supply and demand; it's a permanent, structural deficit that will only worsen as the population ages and chronic diseases proliferate. Xenotransplantation offers a potential exit ramp. "The shortage of donor organs remains one of the greatest crises in modern medicine," a 2025 review in Signal Transduction and Targeted Therapy noted. "Lung transplantation, in particular, is limited by the scarcity of suitable donors and the high rate of early graft dysfunction even in allogeneic settings. Xenotransplantation … offers a potential solution"[reference:17].
Significant hurdles remain. The 9‑day survival in a brain‑dead recipient is a far cry from long‑term function in a living patient. The risk of zoonotic infection—transmission of animal viruses to humans—must be carefully managed. And the ethical questions surrounding the use of gene‑edited animals for organ harvesting are far from resolved. But the momentum is undeniable. As one researcher put it, "Gene‑edited pig lungs might someday expand the donor pool and save lives"[reference:18]. The first clinical trials in living patients are likely within the decade.
The AI and Computational Modeling Revolution: Making EVLP Smarter
If gene editing is the scalpel, artificial intelligence is the GPS. A 2026 study in Frontiers in Physiology introduced a computational physiological model (CPM) of lungs on EVLP that integrates established principles of lung mechanics, gas exchange, and perfusion with clinical input data[reference:19]. The model provides mechanistic insight into ex vivo lung physiology and quantifies intrinsic properties such as alveolar dead space and intrapulmonary shunting—parameters that are critical for optimizing ventilation and perfusion settings but impossible to measure directly in real time. "This CPM enhances understanding of ex vivo lung physiology, which may lead to less injurious EVLP management and support safe, extended‑duration EVLP," the authors concluded[reference:20].
The practical implications are significant. Current EVLP protocols use standardized ventilation and perfusion settings, ignoring donor‑specific lung properties except for height and ideal weight. This one‑size‑fits‑all approach can inadvertently injure certain lungs, particularly when FiO2 is transiently increased to 100% during oxygenation challenges. A personalized, model‑guided approach could reduce ventilator‑induced lung injury, extend the safe duration of EVLP, and increase the number of lungs that ultimately make it to transplant. The model has already been validated against clinical EVLP data, with simulation results closely aligning with clinical measurements of left atrial partial oxygen pressure (root mean squared error of just 6.4 mmHg). Sensitivity analysis and uncertainty quantification further elucidated key determinants of oxygen and carbon dioxide dynamics, including inspired oxygen fraction, intrapulmonary shunt, dead space, and perfusate flow.
AI is also being deployed to predict which lungs are most likely to benefit from EVLP. A 2025 study used machine learning to analyze 82 extended‑criteria donor lungs assessed by remote, centralized EVLP and identified objective criteria—vascular permeability, static compliance, and oxygen transfer—that were associated with the decision to transplant[reference:21]. The study found that 2‑hour EVLP assessments may be sufficient for determining donor quality, potentially streamlining the evaluation process and reducing the time lungs spend on the perfusion circuit. "We provide objective criteria that are associated with the decision to use donor from brain death and DCD lungs assessed by rc‑EVLP," the authors noted[reference:22]. As AI models become more sophisticated and datasets grow larger, the ability to predict which lungs will function well after transplant—and which will not—will only improve.
The Organ Shortage Crisis: Why All of This Matters
It's easy to get lost in the technical details of EVLP, CRISPR, and xenotransplantation and lose sight of why this research matters. The answer is simple: people are dying while waiting for lungs that never come. In the UK alone, more than 8,000 people are on the transplant waiting list, and waitlist mortality hovers around 30% in many regions[reference:23][reference:24]. The situation is similar in the United States, where lungs recovered from donation after circulatory death (DCD) are "markedly underutilized" despite evidence that expanded DCD transplantation reduces waitlist mortality and increases transplant rates[reference:25].
The reasons for the shortage are multifaceted. The donor pool is smaller than it could be, partly because family consent rates are lower than they should be, and partly because many potential donors are excluded due to health conditions, age, or the circumstances of death[reference:26]. But a major driver is simply that many organs are declined because there isn't enough time to properly assess them. "Currently, many organs are declined simply because there is not enough time to carry out the tests needed to be confident they will work well for a recipient," explains NHS Blood and Transplant[reference:27]. "The ARC model gives clinicians more time, more data, and safer conditions to make those decisions."
The Assessment and Recovery Centres (ARCs) pilot programme, launched by NHS Blood and Transplant in March 2026, is a direct response to this crisis. The first lung ARC opened in March 2026, with Harefield Hospital in London selected as one of the pilot sites. "With more than 8,000 people on the transplant waiting list, a fully established ARC network could deliver up to 750 additional transplants each year—potentially transforming outcomes for hundreds of patients"[reference:28]. The ARC model is designed to evolve: if successful, NHSBT plans to expand ARCs into dedicated facilities capable not only of preserving and assessing organs but also reconditioning them through surgical repair, targeted medications, or other advanced therapies[reference:29]. "There is an urgent need to innovate in organ utilisation," said Anthony Clarkson, NHSBT director of organ and tissue donation and transplantation. "Survival on the transplant waitlist is a daily struggle, and hundreds of patients will die this year before they can receive a life‑saving transplant. Donation alone cannot close the gap"[reference:30].
The economic case for investing in organ repair technologies is equally compelling. The Composite Allocation Score (CAS) and continuous distribution system, implemented in 2026, have already increased transplant rates and reduced waitlist deaths without affecting short‑term survival after transplant[reference:31]. A fully realized network of organ repair centers—equipped with EVLP, gene therapy capabilities, and AI‑driven assessment tools—could save the healthcare system billions in dialysis, ICU stays, and long‑term disability costs while dramatically improving quality of life for transplant recipients. As Dr. Zubir Ahmed, the UK's Health Innovation and Safety Minister, put it: "This programme could mean saving and transforming hundreds of lives that might otherwise have been lost. As a transplant surgeon, I know first‑hand what that can mean for patients and families"[reference:32].
The Preservation Frontier: Keeping Lungs Alive Longer
One of the most operationally significant advances of the past few years has been in organ preservation. The traditional method—static cold storage at 1–4°C—has been the standard for decades, but it severely limits the time available for transport, assessment, and preparation. A 2026 study from NewYork‑Presbyterian and Columbia University has now validated a game‑changing alternative: keeping donor lungs at 10°C rather than on ice. The retrospective analysis of 263 consecutive lung transplants found no differences in patient outcomes—including primary graft dysfunction, days on ECMO, duration of mechanical ventilation, and 30‑day, 90‑day, and 1‑year mortality—between lungs preserved on ice and those stored at 10°C for various lengths of time[reference:33]. The median total preservation time for the under‑ice cohort was five hours, versus more than 10 hours for the 10°C cohort—and in some cases, lungs were preserved at 10°C for up to 14 hours with no apparent detriment.
"There's evidence going back over 30 years ago that the best temperature to preserve lungs was 10°C, although logistically it was never implemented anywhere," said Dr. Frank D'Ovidio, senior author of the paper. "After a more recent clinical trial in Toronto validated the evidence and proved lungs could remain viable for longer at 10°C, Dr. D'Ovidio and team adopted the temperature as their standard"[reference:34]. The operational benefits are substantial: the 10°C preservation unit allows surgical teams to schedule transplants during daylight hours rather than in the middle of the night, reduces the number of patients called in unnecessarily for transplants that don't proceed, and gives clinicians more time to perform necessary tests and prepare the recipient. "There are definite resource benefits, logistics benefits, and treatment benefits for patients, and overall, the outcomes have been extremely favorable," D'Ovidio said[reference:35].
Meanwhile, researchers are exploring even more advanced preservation techniques. A 2026 study in the Journal of Surgical Research tested hypothermic machine perfusion (HMP) at 10°C for lung preservation—a technique widely used for kidneys, livers, and hearts but previously unproven for lungs. The results were mixed: while HMP was technically feasible and preserved oxygen content, it induced significantly greater edema than static cold storage when performed without ventilation or oxygenation[reference:36]. The findings suggest that direct transfer of HMP protocols from abdominal organs to the lung may require adaptation, but they also point the way toward more sophisticated preservation strategies that could one day extend the viable window for lung transplantation to 24 hours or more.
The Total Artificial Lung: A Bridge to Nowhere—and Everywhere
Sometimes, the only way to save a patient is to remove their lungs entirely—and then figure out how to keep them alive without them. In January 2026, surgeons at Northwestern Medicine did exactly that. They supported a critically ill patient for 48 hours with no lungs at all, using a total artificial lung (TAL) system designed to temporarily replace key functions of the lungs while also maintaining stable blood flow through the heart and body[reference:37]. The patient, who had developed a rapidly progressive, necrotizing pneumonia and overwhelming sepsis that was resistant to all antibiotics, was too unstable to undergo lung removal and transplant in a single setting. "He had developed an infection of his lungs that just could not be treated with any antibiotics because it was resistant to everything," said Dr. Ankit Bharat, chief of thoracic surgery at Northwestern Medicine[reference:38].
The solution was audacious: remove both lungs to eliminate the infectious source, support the patient with an artificial lung system for 48 hours to stabilize their condition, and then perform a double‑lung transplant. The TAL system was engineered to do more than oxygenate blood; it was designed to support circulation in the absence of lungs by helping maintain balanced blood flow through the heart—an essential requirement for survival after bilateral pneumonectomy. The design incorporated a flow‑adaptive shunt that compensated for the loss of the lung's blood vessel network, dual pathways to drain blood from the body and return oxygenated blood to the heart, and temporary internal supports—including saline‑filled tissue expanders (breast implants) commonly used in reconstructive surgery—to stabilize the heart's position until transplantation[reference:39].
The procedure was a success. The patient survived the 48‑hour lungless interval and received a double‑lung transplant. The case, published in Cell Press journal Med, represents a new paradigm for managing the sickest acute respiratory distress syndrome (ARDS) patients—those for whom the lungs themselves have become the source of relentless infection and inflammation. "For the sickest ARDS patients, clinicians often rely on prolonged life support and time, hoping the lungs can recover," the report notes. "But in some cases, the lungs themselves become the source of relentless infection and inflammation, driving organ failure and leaving no path forward unless the diseased lungs can be removed and replaced"[reference:40]. The total artificial lung offers a bridge—a way to stabilize patients who would otherwise die while waiting for donor lungs that may never come. It's the most extreme expression of Bacchetta's original insight: that with the right support, even the most damaged lungs—or no lungs at all—can be a stepping stone to survival.
The Road Ahead: What Does 2030 Look Like for Lung Transplantation?
If current trends continue, the lung transplantation landscape of 2030 will look radically different from today. Imagine a donor lung that arrives at a centralized Assessment and Recovery Centre, where it is placed on an AI‑guided EVLP circuit. A computational model, tailored to the lung's unique physiology, optimizes ventilation and perfusion settings to minimize injury. A gene therapy vector—delivered via lipid nanoparticles during EVLP—modulates the lung's immune profile, reducing the risk of rejection and ischemia‑reperfusion injury. The lung is preserved at 10°C, giving the surgical team time to prepare the recipient during daylight hours. If the lung is too damaged to recover, it may still be used as a bridge—or, in the most extreme cases, a total artificial lung system may support the patient until a suitable organ becomes available. And for patients who cannot find a human donor, a gene‑edited pig lung—customized to avoid hyperacute rejection—may offer a viable alternative.
This is not science fiction. Every piece of this pipeline exists today in some form. EVLP is a clinical reality. Gene therapy and CRISPR editing have been demonstrated in human lungs ex vivo. 10°C preservation is becoming standard at leading transplant centers. Remote, centralized EVLP is expanding the donor pool in real‑world settings. Xenotransplantation has achieved proof‑of‑concept survival in human recipients. And a total artificial lung has kept a patient alive for 48 hours with no lungs at all. The pieces are in place. The challenge now is integration—and scaling.
The economic and human stakes could not be higher. The global shortage of transplantable lungs is not a temporary mismatch; it's a permanent, structural deficit. More than 8,000 people are on the waiting list in the UK alone. Waitlist mortality remains unacceptably high. And the donor population is aging, meaning that more organs are coming from extended‑criteria donors who require careful assessment and often active rehabilitation. The technologies described in this article—EVLP, gene therapy, AI‑guided perfusion, advanced preservation, and xenotransplantation—are not luxuries. They are necessities. They are the tools we need to close the gap between the number of people who need lungs and the number of lungs available to transplant.
When Bacchetta and his colleagues hooked a damaged pig lung up to a living pig's bloodstream in 2019, they were asking a simple question: can we give damaged lungs more time to heal? The answer was yes—and that answer has spawned an entire field of research dedicated to mending harmed contributor lungs. The next question is whether we have the will—and the resources—to bring these technologies to every patient who needs them. The science is ready. The patients are waiting. The only thing missing is the commitment to make it happen. As Bacchetta said back in 2019, "We were … hunting down an approach to stretch out the capacity to give life‑sparing treatment to patients." That hunt is far from over—but the trail is now well marked, and the destination is finally in sight.
Key Takeaways: The Revolution in Lung Repair and Transplantation
- The 2019 Bacchetta study was a watershed moment: Damaged pig lungs hooked up to a living recipient's bloodstream recovered over three days and functioned 30 times better than controls, proving that a living bioreactor could heal severely injured lungs.
- Ex vivo lung perfusion (EVLP) has become a clinical workhorse: EVLP allows assessment and active rehabilitation of marginal donor lungs. Remote, centralized EVLP has achieved 56% transplantation rates with 93% 1‑year survival and 100% 1‑year survival for DCD lungs.
- Gene therapy and CRISPR editing are entering the EVLP toolkit: The LifeLUNG project and other initiatives are developing advanced delivery vehicles—AAV, virus‑like particles, lipid nanoparticles—to genetically modulate donor lungs during EVLP, reducing rejection and ischemia‑reperfusion injury.
- Xenotransplantation has achieved proof‑of‑concept in humans: In 2025, a six‑gene‑edited pig lung functioned for nine days in a brain‑dead human recipient. An 11‑gene‑edited pig lung achieved 33‑day survival in preclinical models.
- AI and computational modeling are making EVLP smarter: Personalized physiological models can optimize ventilation and perfusion settings, reducing ventilator‑induced injury and extending safe EVLP duration.
- 10°C preservation is becoming the new standard: A 2026 study of 263 transplants found no differences in outcomes between ice‑preserved lungs and those stored at 10°C—with median preservation times doubling from 5 to >10 hours.
- A total artificial lung kept a patient alive for 48 hours with no lungs: Northwestern Medicine surgeons removed both lungs from a septic patient, supported him with an artificial lung system, and then performed a successful double‑lung transplant.
- The organ shortage crisis is acute: More than 8,000 people are on the UK waiting list alone. The NHS's ARC pilot programme aims to deliver up to 750 additional transplants annually through centralized organ assessment and recovery.
- Thermal preconditioning offers a non‑pharmacologic repair strategy: Brief exposure to 41.5°C during EVLP induces a protective heat shock response, reducing edema and improving compliance in damaged lungs.
- The pieces are in place—integration is the next frontier: The 2030 vision includes AI‑guided EVLP, gene therapy, advanced preservation, and xenotransplantation working together to close the gap between donor supply and patient demand.
Sources and Further Reading
- Nature Communications (2019): Xenogeneic cross‑circulation for extracorporeal recovery of injured human lungs — Original Bacchetta study with 30‑fold improvement in lung function.
- Frontiers in Physiology (2026): Computational physiological modeling for lung‑specific ventilation and perfusion management in EVLP — AI‑guided optimization of EVLP settings.
- JoVE (2025): Thermal Preconditioning During Ex‑vivo Lung Perfusion for Rehabilitation of Damaged Lung Grafts — 41.5°C heat stress induces protective heat shock response.
- JTCVS Open (2025): Outcomes associated with remote, centralized EVLP for donor lungs in a real‑world setting — 56% transplant rate, 93% 1‑year survival, 100% DCD survival.
- Nature Medicine (2025): First pig‑to‑human lung xenotransplantation using six‑gene‑edited Bama Xiang pig — 9‑day survival in brain‑dead recipient.
- Human Gene Therapy (2024): CRISPR‑Cas Genome Editing in Ex Vivo Human Lungs — First platform for testing genome editing in human lungs ex vivo.
- LifeLUNG Project (2025‑ongoing): Improving Life expectancy of LUNG transplant recipients through innovative ex vivo perfusion gene therapy — EU‑funded initiative combining EVLP and gene therapy.
- NewYork‑Presbyterian/Columbia (2026): Keeping lung allografts at 10°C allows increased preservation time — 263‑patient study showing non‑inferior outcomes, median preservation doubled.
- Northwestern Medicine (2026): Total artificial lung system keeps patient alive for 48 hours after lung removal — First successful bilateral pneumonectomy with artificial lung bridge to transplant.
- NHS Blood and Transplant (2026): Assessment and Recovery Centres pilot programme — Up to 750 additional transplants annually, 8,000+ on waiting list.
- JTCVS Open (2025): Regadenoson in the rehabilitation of marginal donor lungs on EVLP — Multicenter RCT showing safety but no significant increase in utilization.
- Journal of Surgical Research (2026): Feasibility of Lung Hypothermic Perfusion Without Ventilation — HMP induces edema, requires protocol adaptation for lungs.
- Lund University: Advanced engineered MSC‑Therapies for Lung Transplantation — CRISPR‑engineered stem cells to promote immune tolerance.
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