Industry Frontier | Researchers transform type A blood donor lungs into universal blood type donor lungs through enzymatic treatment

Recently, Canadian researchers say they have found a way to help people who would otherwise languish on the organ transplant list. In their new study, they detail converting lungs from people with type A blood into lungs that can be donated to anyone without severely damaging them or causing acute rejection. Assuming the team's work is further validated and tested to be safe, it could one day expand the number of universal donor lungs.

Donated organs and tissues must be carefully reviewed to ensure a match between donor and recipient. One of these important criteria is blood type, as the body's immune system quickly attacks incompatible types of antigens in the blood or organs. People with type O blood can donate to others because they lack the antigens that trigger other people's immune systems, while people with type AB blood can receive organs from other people.

Unfortunately, there are only so many organs available from universal donors at any one time, which may further exacerbate donor shortages for some people who need transplants. For example, studies have shown that potential organ recipients with type O blood (who can only get organs from other type O donors) spend more time on the waiting list than others and are therefore more likely to die. Mismatched organs may even be thrown away without seeing any use at all. The new study, published in the journal Science Translational Medicine, may one day help resolve these questions.

Researchers from the University of Toronto and other Canadian universities collaborated on the study. Based on earlier research, they speculated that a combination of two enzymes could largely remove antigens associated with type A blood in donated lungs, effectively converting them into type O lungs. They tested the process first on human tissue from the aorta, the body's largest artery, and then on eight donated human lungs that had earlier been deemed unsuitable for transplant.

In both tests, the team's mixture appeared to be effective. Within 4 hours of the enzyme being injected into the lungs, more than 97% of type A antigens were cleared from the lungs, with no obvious signs of lung toxicity. The team then exposed the lungs to plasma from Type O individuals and recorded minimal responses from normally hostile antibodies, suggesting that these people's lungs could safely tolerate it. According to study author Marcelo Cypel, a professor of surgery at the University of Toronto, this process should have a similar effect on any donated organ, not just lungs.

These findings are based on smaller sample sizes and should be treated with caution. It will take more research, and most importantly clinical trials and follow-up data on people who receive these transformed organs, to truly know whether this approach is safe in the long term. But the team hopes to begin clinical trials within the next 12 to 18 months, and if the results pan out, their work could save more lives. Today, about 55% of donated organs come from type O donors, and this process can convert about 80% of organs into universal donors.

"Many times, we are unable to transplant the sickest patients to the next donor. Therefore, some patients die on the waiting list. Some patients have to wait a long time," Cypel said. If we remove ABOs as a barrier to matching, we will take a giant step toward equity in organ donor allocation.

Literature source: https://www.science.org/doi/10.1126/scitranslmed.abm7190