Cypel hopes increasing the number of global donors will make more lungs available to more people and make the process fairer. “Today we have a separate list of patient A, patient B, patient O, and we don’t necessarily need a transplant. [to] the sickest,” he said. And even if a pair of donor lungs match that person’s blood type, they may not be the right size for them. Too small and they won’t provide enough oxygen. Too big and they won’t fit the bust.
Even worse, only about 20 percent the donor lungs are healthy enough to use. Some are traumatized by being on ventilators for too long, others have an infection, or simply because the donor is too far away for their organs to reach the patient in time. But Cypel thinks technologies like EVLP and blood type switching could dramatically improve transplant rates. “Currently in North America, we do about 2,500 lung transplants a year. I think we can double that number,” he said.
To test their idea, Wang, Cypel and their collaborators worked with Stephen Withers, a chemist at the University of British Columbia, to identify a specific set of molecular tools. Withers tested thousands of enzymes in the human gut and found two, FpGalNAc deacetylase and FpGalactosaminidase, that normally help the body create energy by digesting sugar antigens on the intestinal wall. Those sugars are similar to A antigens, which means that these enzymes are uniquely suited to perform a highly specialized task: Acting like molecular editors, they monitor these antigens. on the cell, shred them and leave that O-core structure.
Using a set of donated lungs that once belonged to a person with blood type A, Wang and Cypel injected a small amount of the enzyme into the tissue. The team then performed antibody staining, marking the remaining antigens so they could see how successful the enzymes were. Within an hour, more than 90 percent of that A antigen had been shredded. After four hours, 97 percent were gone.
Next, the team assessed the lungs using the same parameters that the transplant team would use, assessing factors such as airway pressure, blood gases, and lung inflammation. Despite their transformation, the lungs are healthy. “To have something work so well in such a short amount of time in a viable dose — it’s amazing when it happens,” says Wang.
This study is just a proof of concept, aiming to show that such a feat is possible, cost-effective, and effective fast enough to perform in a real-life transplant scenario. . But they didn’t try tissue culture, but focused on the A antigen. (The team is currently searching for the right enzymes to perform the same sniping and searching function on the B antigens.) A question to ask. It turns out whether the body will immediately reject the modified lung. Another issue is whether those A antigens regrow and trigger a dangerous immune response when they do.
“This study and the reported results are particularly important, because of graft-versus-donor antibody-induced graft diseases,” said Marilia Cascalho, an immunologist at the University of Michigan who was not involved in the study. It is one of the most difficult diseases to treat.
