Damaged Human Lungs Restored for Transplantation

Yorkshire swine (Edward Headington, Flickr. https://flic.kr/p/fvfie6)

23 Jan 2023. A research team demonstrated the feasibility of connecting anesthetized pigs to human lungs deemed unfit for transplants, for recovering the lungs to transplant quality. A team from Columbia, Vanderbilt, and other universities and the company Xylyx Bio Inc. in Brooklyn, New York demonstrated the technique, announced today by the company, and published earlier in The Journal of Heart and Lung Transplantation (paid subscription required).

The researchers are seeking to improve the supply of organs available for transplant, a particular problem for lungs, where according to data cited by Xylyx Bio, 80 percent of donated lungs are not considered of suitable quality for transplant. Moreover, says the company, damage to lungs in many cases is from reversible conditions, making repair of many damaged lungs technically possible.  Lung transplants are often the only way to treat patients with end-stage lung disease, the most severe form of lung diseases, such as chronic obstructive pulmonary disease or COPD, emphysema, and chronic bronchitis.

Biomedical engineering labs at Columbia University in New York and Vanderbilt University in Nashville designed the process for damaged lung recovery. As reported in Science & Enterprise in May 2019, a team from the labs of Gordana Vunjak-Novakovic at Columbia and Matthew Bacchetta at Vanderbilt built on current techniques for ex vivo, or outside-the-body, lung perfusion for improving the state of lower-quality lungs for transplant, to enable restoring damaged lungs that did not meet transplant standards. At the time, the team demonstrated on pigs techniques for restoring damage from gastric aspiration, where acids in the stomach burn lung and airway tissue.

Synthetic cobra venom proteins

The researchers in this case are seeking to establish a standard, feasible, and reproducible process for recovering damaged lungs. In their study, Vunjak-Novakovic, Bachetta, and colleagues applied their process called xenogeneic cross-circulation, where whole blood from anesthetized animals, in this case Yorkshire and Landrace breed swine, is sent from the pigs into nine human lungs rated as too damaged for transplant, then back to the pigs. The animals are treated with immunosuppressive drugs, as well as synthetic cobra venom proteins that deplete the complement system, part of the immune system protecting against invading pathogens. The team tested lung quality every six hours with bronchoscope observation and microscope inspection.

After 24 hours of xenogeneic cross-circulation, say the authors, capacity of air sacs in the nine damaged lungs increased by 158 percent and dynamic pulmonary compliance, a measure of lung elasticity, increased by 127 percent. Airway and blood pressures in the lungs, and lung weight remained stable. In addition, the structure of the lungs and their ability to exchange oxygen and carbon dioxide between the lungs and blood stream remained intact.

Vunjak-Novakovic founded Xylyx Bio in 2016 with John O’Neill, now the company’s chief scientist. Vunjak-Novakovic and Bacchetta serve on Xylyx Bio board. The company offers a service for repair and recovery of damaged donor organs, including lungs, for transplant, building on the xenogeneic cross-circulation technology.

“Xenogeneic cross-circulation is proving to be a robust method for ex vivo support, evaluation, and improvement of donor lungs,” says Bachetta in a Xylyx Bio statement released through Cision. “Our technique,” adds O’Neill, “provides donor organs a healthy blood supply with sustained multi-system physiological regulation, a powerful advantage that is unique in the field.”

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