Blood Type Conversion Breakthrough Could Make Universal Lung Transplants Possible

Millions of people around the world are in need of a major organ transplant, but very few are able to find a living donor. More than 106,000 Americans are waiting for a new agency, and 17 people die every day waiting for a transplant. This is especially true during COVID, where the disease has destroyed the respiratory health of thousands of people and left their lungs devastated. More and more people need a lung transplant — but there are simply too few lungs to go around to save everyone.

One of the biggest obstacles to transplants is also a simple one: matching blood type. This is especially true for the heart and lungs, which are more sensitive than other organs to mismatched blood types, says Dr. Alexander Krupnick, a lung transplant surgeon at the University of Maryland Medical Center.

But new research in Canada promises to address this incompatibility obstacle by doing something rather extraordinary: converting an organ’s native blood type to a universal blood type.

In a new study published on Wednesday in Medical translation scienceResearchers in Toronto were able to take donated lungs and separate them from antigens that identify them as blood type A, making the lungs appear as if they came from an O blood type donor – well known as the common donor blood group. (Though technically an O-negative is a true universal donor type.)

The team behind this new paper achieved this breakthrough by flooding the lungs of donated blood with two enzymes that can remove blood group A antigens from the cells lining the blood vessels of the body. organ, where most cases of blood type incompatibility are expressed. Within about 4 hours, enzymes – called FpGalNac deacetylase and FpGalactosaminidase, and naturally produced by our bodies – had cleared more than 97% of the type A antigens from the donated organs.

The team then examined the lungs to see if they lead to a phenomenon known as super-rejection, which occurs when a recipient receives a transfusion of the wrong blood type.

Dr. Aizhou Wang demonstrates delivery of enzymes to the Ex Vivo Lung Perfusion (EVLP) system.

University Health Network

“We basically took two lungs from the same donor,” Dr Marcelo Cypel, surgical director of the Ajmera Transplant Center and co-author of the new study, told The Daily Beast. . “We treat the right lung with enzymes and the left lung we do not treat with enzymes. And then we spilled blood on both words [type] Hey sponsors. We can see that the left lung is working properly [with] there is no sign of refusal to increase the tone, while the other [showed] The signs of hyperechoic rejection are clear.”

Cells treated with these enzymes regenerate type A antigens over time, so this new approach is not a permanent and wholesale way to convert an organ to a new blood type. But it alleviates some of the immune hurdles that patients have to wait for in the first week after transplant surgery.

“If you put an organ in someone and you don’t give them enough immunosuppression, that organ will be rejected within a week due to resistance,” said Krupnick, who was not involved in the new study. body. [research] is a step in the right direction in regulating the immune nature of organs. This is one step of what could be many steps to take any organ and put it in any person with a lower need for immunosuppression.”

In addition to deleting donated organs with her own blood type, Krupnick says the method could be used to address another thorn in the side of transplant medicine. There is a group of genes involved in how our immune system recognizes natural and foreign proteins and pathogens, known as the major histocompatibility complex (MHC). The antigens produced by these genes explain differences in immunity within a population, such as why some individuals succumb to COVID-19 and others show no symptoms what. And MHC can create obstacles when trying to match donors with recipients.

This is one step in what could be many steps to take any organ and put it in any person.

Dr. Alexander Krupnick

“If you peel some [MHC] Antigen, and you put the organ in, and if the antigen comes back in a few weeks, your body reacts to that organ much less than when it was originally transplanted, because the system, says Krupnick Your immune system is more sensitive during the first week, says Krupnick. The enzymes could provide an avenue for doctors to learn how to quench MHC antigens for new organ recipients.

The new findings come at a time when organ transplant research has already made some big strides. In January, a Maryland man undergo the first successful pig-to-human heart transplant. Later that month, surgeons at the University of Alabama at Birmingham Successfully transplanted a pig kidney into the stomach of a brain dead man. These breakthroughs in animal-to-human transplantation are a very different approach to addressing the shortage of transplanted organs, but they will still need a lot of development before we can treat them as a disease. Regular solution to organ transplant. For now, tweaking existing agencies might be an easier way to do with the ones that are actually available.

Cypel says the next phase of research is to test his team’s findings in the mouse study and investigate the kidney as a next target organ, which is one of the organs in top demand with more than 90,000 patients. patients waiting for a kidney transplant.

“We still need to do studies before we can say it can be used in clinical practice,” says Cypel. “But when we get to that point, you know, this could change the way we allocate agencies.”

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