In a step towards increasing access to donor organs, scientists converted blood type A kidneys to blood type O and transplanted them into brain dead.
The kidney, which was transformed into an essentially universal graft organ, worked well for two days before showing signs of rejection. With improvements, this strategy could pave the way for a short wait on the organ donor list.
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Kidney transplants have been a treatment for patients with kidney disease since the 1950s. However, as with all organ transplants, it is somewhat limited by the need to match the donor’s blood type with that of the recipient, as well as the requirement to find an organ of the right size geographically close enough to be transplanted in time.
Humans have four major blood groups: A, B, AB, O-, and the immune system of a person with one blood type may respond to another type. For example, a transplant candidate with type O blood can only receive type donor kidneys, but people with blood types A, B, or AB can also receive kidney types. This is because each blood type is defined by an immune trigger substance called an antigen. oBlood is lacking in these antigens, so other blood types can be administered universally, while causing the type O immune system.
However, in the late 1980s, scientists developed a method for transplanting non-ABOI organs, organs from donors with one blood type to donors with incompatible blood types. However, this process is demanding and takes several days. Then, in 2022, researchers could develop enzyme-based therapy protocols and convert organs into “universal” implants called enzyme conversion O or ECO.
“The ECO process is demonstrated for the lungs,” Steartor Stephen Withers, professor emeritus of biochemistry at the University of British Columbia, told Live Science in an email. “We hope it helps all other organs – it should!” (Another research group reported that ECO is used to convert the kidneys, but they started with blood type B kidneys in the experiment.)
The Wizards were part of the 2022 team that converted lungs from Type A to Type O. However, the team did not implant eco-lung into humans in the proof-of-concept experiment. In a new study, Wizards and colleagues converted the kidneys, which were deemed unsuitable for implantation, to kidneys that took about two hours by perfusing special fluids into the kidneys.
“Perfusion devices and organ preservation solutions are very commonly used to keep organs in good condition during donations and transplants,” Wizards explained. To convert organs, researchers placed certain enzymes in the perfusate to remove blood group antigens that could cause rejection.
“In this way, the organs are then recognized and not targeted by anti-A antibodies present in the recipient’s bloodstream,” Wizards said. This procedure does not permanently remove any problematic antigen organs, but it can help to stem the worst reactions of the immune system.
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To see if the kidneys could escape immediate human rejection, the team turned to brain dead recipients whose families had agreed to the study. The team transplanted the eco kidneys into the recipient, and the recipient carried large amounts of anti-A antibodies.
In a typical transplant, antibody therapy is administered to the recipient before and after the transplant, and antibody therapy is administered to prevent rapid “over” rejection. However, the therapy was not applied because the researchers wanted to test whether creating eco-kidneys would prevent early rejection.
“We had to understand how things went,” Wizards said. They wanted to monitor how quickly the antigen reappeared in the kidneys and how long the recipient’s body could withstand.
Researchers found that the eco kidneys worked well for two days after transplant and there were no signs of rejection. The immune response to the new kidney appeared on day 3. This is when the eco kidneys begin to create new A antigens.
“In actual clinical implants, there are many steps that can be applied to minimize early antibody-mediated rejection, including optimized immunosuppression,” Wizards said. These methods may allow long-term resistance to transplants, if standard care for any organ transplant, and also used in eco-kidneys.
It is important for researchers to convert from one blood type to another to increase patient access to donor organs. This is especially important for “type O transplant candidates that make up more than 50% of the waiting list and usually wait two to four years longer than other blood types.”
The eco-kidney has been successfully transplanted, but the development of this transplant process is still in its early stages.
“I don’t know if this applies universally,” Wizards said. “But that’s certainly a possibility.”
This article is for informational purposes only and is not intended to provide medical advice.
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