In China, a lung from a genetically modified pig was transplanted into a brain-dead person for the first time in the world. The transplant worked for four days in a 39-year-old brain-dead man. The results of the study are published in Nature Medicine.
The patient was a man who was already “brain dead” — meaning his brain had completely stopped working and he could not live without life support. This condition is often used in scientific research to avoid risking the lives of patients who could recover.
Lungs are considered one of the most difficult organs to transplant due to their dense vascular network, which increases the risk of blood clots and rejection. To reduce the risk, three genes that provoke an immune response were removed from the donor pig and three human protective genes were added.
Lungs are a very, very difficult organ to transplant, even more difficult than the heart or kidneys. Why? Because they have so many tiny blood vessels, like a spider's web. And that's why there's a very high risk: blood clots (when blood clots and blocks these tiny vessels, which can stop the lung from working) and rejection (when the patient's immune system recognizes the new lung as something foreign and starts attacking it, trying to destroy it). To reduce these risks, scientists genetically modified a donor pig. They removed three genes in the pig, that is, they “turned off” the signals that scream “I am a foreigner!” And conversely, they added three human genes, which, in essence, were supposed to “disguise” the pig lung as a human one and protect it from rejection.
There were no signs of hyperactive rejection or infection in the first few days after surgery. However, after 48 hours, tissue damage occurred due to the temporary lack of oxygen during the procedure (ischemic-reperfusion injury) and antibody attack, leading to microvascular thrombosis. By the time the study was stopped (after 96 hours), these changes had begun to subside, but the study was stopped at the request of the patient's family.
At first, everything went quite well, and it was very encouraging! In the first two days after the surgery, the doctors saw no signs of the body attacking the new organ too quickly and too strongly, or any serious infections. But after 48 hours, problems started: the pig's lung tissue was damaged. This was caused by two main reasons:
1. “Ischemia-reperfusion injury”: This is a complex term that simply means damage to an organ that occurs when it has been deprived of oxygen for a period of time (such as during a transplant) and then oxygen is re-introduced to it with the blood.
2. “Antibody attack”: Unfortunately, the patient's immune system did start to secrete special proteins called antibodies that attacked the new lung. This led to the formation of tiny blood clots in the same small vessels we talked about earlier, preventing the lung from working properly.
Interestingly, by the end of the study, these negative lung changes had begun to diminish, meaning that perhaps things could improve.
Experts believe this work paves the way for future clinical trials. If the technology is refined, pig lungs could be a chance for life for patients with terminal respiratory diseases who currently die waiting for donor organs.
