
Researchers have successfully changed the blood type of a donated human lung by treating it with enzymes, in an important step towards making universal donor organs.
“We still have a way to go to show safety in clinical trials,” says at the University of Toronto, Canada. “But assuming that the results on clinical trials are similar to the results we observed here, this will be a major breakthrough.”
Blood types are largely defined by the presence or absence of certain sugar molecules called antigens on the surface of cells. These can occur not just on the cells of the blood itself, but also other tissues, such as those in the lung. If an antigen isn’t recognised by the body’s immune system, it will mount an attack on these cells.
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This leads to the rejection of transplanted organs from a donor with a different blood type. People with rare blood types often have to wait longer for transplants because the pool of potential donors is smaller, and some die while they are on the waiting list.
People with the most common blood type, O, lack these antigens on their cells, so their organs can be accepted by people with other blood types. If all donor organs could be made type O, for example the lungs from someone with blood type A, this could be a help.
To try this, Cypel and his team used a pair of enzymes that are normally found in the human gut to digest sugars. They found that the enzymes removed more than 99 per cent of type A antigens from red blood cells and 97 per cent from lungs from a type A donor in 4 hours. This meant the cells had been effectively changed to blood type O.
After this treatment, the altered lungs were kept alive using a system known as ex-vivo lung perfusion, which supplies organs with nourishing fluid so they are ready for transplantation.
To simulate a transplant, Cypel’s team then added type O blood, which contains antibodies that would attack type A antigens, to the fluid supplying the lungs. The treated lungs had minimal antibody damage compared with the untreated lungs. “When we perfused the lung with old blood, there was no sign of rejection or organ dysfunction,” says Cypel.
Although cells stripped of antigens tend to produce new ones over time, Cypel is hoping that the lack of antigens will last long enough for the body to get through the perilous first few days and weeks after a transplant.
But the study only looked at the effects of a simulated transplantation over the short term, which isn’t enough time to assess whether the resurfaced antigens could eventually have a negative effect, says at Royal Papworth Hospital, Cambridge, UK. “We can’t [yet] say whether re-exposure of these antigens or the changes that come with that are going to be deleterious in the long run or not.”
Cypel and his team now intend to test the process in animals. If the organs prove safe and well-tolerated in the long term, the method might prove suitable for humans.
“This may offer the opportunity of a transplant if all the caveats are met when it’s translated into clinical care,” says Parmar. “If this then means that we can offer more people transplantation, then we’ve got a real opportunity to make a difference in terms of waiting list mortality.”
Science Translational Medicine