🫁 Lung 2.0

Last updated 2/11/20

Lung 2.0 Progress: 52.5%

52%

Phase 1: Functional external synthetic replacement lung

Proof of ConceptAnimal Testing/R&DClinical TrialsApprovalMass Adoption
CompletedCompletedCompletedCompletedCompleted
100% Completed

Phase 2: Functional internal synthetic replacement lung

Proof of ConceptAnimal Testing/R&DClinical TrialsApprovalMass Adoption
CompletedIn Progress
30% Completed

Phase 3: Effective respiratory stem cell therapies

Proof of ConceptAnimal Testing/R&DClinical TrialsApprovalMass Adoption
CompletedCompletedIn Progress
50% Completed

Phase 4: Transplantable lab grown lungs

Proof of ConceptAnimal Testing/R&DClinical TrialsApprovalMass Adoption
CompletedIn Progress
30% Completed

    Transplanting the human lung


    Lung transplantation is the process through which old failing lungs are surgically replaced with donor lungs. The procedure was the fourth most common transplant in 2020.

    Lung Transplant Catalysts

    • Lung transplants are most commonly caused by COPD (27%) followed by various forms of fibrosis. 
    • The second largest cause, cystic fibrosis, requires the patient to receive a double lung transplant. 
    • High blood pressure in the lungs (pulmonary hypertension) is the other main cause of lung transplants. 
    • Some severe cardiac diseases can cause a heart and lung transplant. 

    Lung Transplant Criteria

    • Have one of the life threatening conditions listed above
    • Cancer free for at least 5 years
    • Cigarette/smoke free for at least 6 months
    • Blood type match with donor
    • Age match with donor 
    • Chest cavity dimensions must match up with donor lungs
    • Tissue type match with donor (urgency may outweigh compatibility in this area)

    Transplant survival rates (2008)

    • 1 Year: 83.6%
    • 2 Years: 53.4%
    • 3 Years: 28.4%

    Post-transplantation, patients have two serious issues to contend with. Because nerve connections are severed during the procedure, patients can no long feel when their lungs are congested or have the urge to cough. This means that lung transplant recipients have to consciously clear their lungs for the rest of their lives. Secondly, chronic rejection of the donor lungs can occour even after taking immunosuppressants and occurs in 50% of patients

    In 2020, complications from COVID-19 have put a strain on the lung transplantation process. Fibrosis from COVID-19 can affect people in their 20s, not just the elderly. As a reaction to the virus, fluid will build up in tiny air sacs in the lungs depriving them of of oxygen and often lead to organ failure. According to experts. it is unclear why COVID causes fibrosis in some but not in others. If the fibrosis is severe enough a lung transplant is need, although ventilators can generally keep the patient alive long enough to recover. Of everyone infected with COVID-19, 40% develop ARDS and 20% of those cases are severe.

    Recreating the human lung


    Compared to other organs, we are remarkably close to lab grown lungs hitting the transplant market. On the synthetic side there has been few breakthroughs since the invention of the ventilator 

    Biological Recreation

    In 2014 a University of Texas based team announced that their lab had grown a human lung for the very first time. The project began with pig lung recreation and was scaled to to human lungs. Stem cells grew the lung from an existing human lung scaffolding reduced to the connective tissue (collagen and elastin) rather than completely from scratch. Inside of a bioreactor, the maturation process took 4 weeks to grow to completion. According to lead researcher Dr. Joan Nichols, “UTMB’s work represents a landmark in regenerative engineering, but the reality of lab-engineered lungs being used in transplants could be at least 12 years away, Nichols says. The next phase of the research will be to test lab-grown lungs in pigs.”

    In 2018, that next phase was realized when a lab grown lung was successfully implanted into a pig. This phase was completed by the same University of Texas team using the exact same scaffolding technique as the previous phase. Two weeks after the transplantation there was a strong network of blood vessels between the lung and host. The pigs received no immunosuppressive therapy and showed no signs of breathing problems or rejections. Dr. Nichols estimates that when lab grown lungs hit the market they will cost around $12k compared to the current $90k cost of a donor lung. In the mean time, researchers need to further 3D bioprinting techniques to solve the scaffolding program so that lab grown organs can truly be mass produced. 

    Synthetic Recreation

    Synthetic recreation of the lung dates all the way to the invention of the ventilator in the 1930s. The basic idea behind ventilators is that a mechanical respiratory system can move air in and out of a patient’s lungs. Typically reserved for patients who are otherwise unable to breath because of a clinical condition, they are also essential for for patients under anesthesia. In the 80s, microprocessor ventilators became the industry standard as they can better monitor a patient’s needs under anesthesia. In the beginning of the 2020, ventilators were a hot commodity in the US after the country failed to properly prepare for the pandemic.

    Because of the large scale complexity of lungs, recreating an implantable synthetic replacement has proven extremely difficult. Ann Arbor based BioLung is trying to supply all of the patients oxygen needs by using the heart’s pumping power. Their system is essentially bypassing the lungs as an oxygen delivery system using ECMO (extracorporeal membrane oxygenation). The BioLung system is implanted into the chest and attached to the heart. The heart will pump blood into the machine and a filtration system then pulls the carbon dioxide out replacing it with oxygen. The BioLung has been in development for eight years and is currently in animal trials. While this product may be able to help patients on the transplant waiting list, it is not a viable solution long term as the strain on the heart increases the risk of heart failure. An external synthetic lung is another big idea in the space. In another synthetic lung project, researchers at the University of Pittsburg combined combined a pump and gas chamber into one small device that can be connected to a patient’s neck with minimal tubing. Although a miniature version of the device worked with rats, the team’s animal trial with sheep had mixed results. 

    Respiratory Technologies


    Steady advances in stem cell research and other forms of biotech make respiratory technology an area to watch. Research in trials now may be helping patients within the decade.

    Stem cell therapies are promising for patients with congenital lung diseases but efficacy has yet to be proven. Most stem cell therapies so far are aimed at treating COPD. Although this treatment has generated a lot of hype, the FDA has not approved any treatments yet and clinical trials have not advanced past phase II. So far, animal trials of COPD stem cell therapy have been promising but human trials have not yet been able to replicate the positive effects. Stem cell therapies could aid the transplantation process, in one study stem cells were found effective in treating BOSa disease caused by the procedure. Another study showed that stem cell therapies can aid the organ transplantation transition period across the board. Finally the most promising stem cell therapy came out of China in 2018 where a patient’s damaged lung was healed significantly over the course of a year. Despite promising results, the official stance by the American Lung Association is a warning against stem cell therapies until long term effects are better understood. Outside of stem cells, biotech research in lung surfactants (the coating of the microscopic air sacs inside of the lung) is accelerating. In 2018, a Stanford University researcher created a synthetic surfactant that significantly increased blood oxygenation in otherwise struggling lungs.