A further step has just been taken towards the use of universal organs. This, in summary, is the contribution of a work recently published in the journal Nature Biomedical Engineering. Led by the team from the Canadian University of British Columbia (UBC), it pursues a goal that is nothing short of ambitious: to overcome the limitations of compatibility in order to reduce waiting times for transplants.
Here, and for the first time in humans with manipulation in vivoThe researchers succeeded in modifying a donor organ initially of group A into a group 0 in order to transplant it into a type 0 patient in a state of brain death, the procedure having been carried out with the agreement of his family, in order to study the manipulation with less risk.
The researchers wanted to act directly on the organ to be transplanted.
Upon reading the university press release, The experiment seems almost simple, since " It's like removing the red paint from a car and revealing the neutral primer., summarizes Stephen G. Withers, professor emeritus in the chemistry department and co-author of the study. In practice, however, it must be admitted that things are a little more complicated.
The researchers wanted to act directly on the organ to be transplanted, in this case a kidney from a type A donor, in order to eliminate the antigens carried by the tissues, cells and vessels of the organ, so that it could be transplanted into a type 0 recipient, which is not compatible.
As a reminder, and to avoid rejection reactions, organ transplants must strictly adhere to a rule dictated by blood types: the donor's blood type must be compatible with the recipient's. In practice, patients with blood type AB, known as universal recipients, are the luckiest since they are compatible with everyone. Furthermore, The A's can only receive A's or O's, the B's only B's or O's, and the big losers are of course the O's, certainly universal donors but only able to receive O's. Consequently, they are the most affected, as they often have to wait longer than others for compatible organs.
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Organ-centered and faster approaches
In order to eventually accelerate these transplants and reduce their waiting times, various teams have been developing techniques for several years that act on the recipient's immune system in order to eliminate circulating antibodies. However, these lengthy and complex protocols remain poorly suited to the urgent context of transplants. Hence the need for faster, organ-directed enzyme conversion approaches.
This time, the researchers used a perfusion device prior to transplantation to circulate a solution containing two digestive enzymes known as conversion enzymes, FpGalNAc deacetylase and FpGalactosaminidase, through the kidney. already identified by the same UBC team in 2019 Then tested in 2022but only ex vivo on lungs by another Canadian team from Toronto (Ontario) which were not subsequently transplanted but left in the perfusion device.
View of the kidney, before transplantation, in a perfusion device circulating a solution containing converting enzymes. Credits: Nature Biomedical Engineering
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The kidney functioned for two days without any signs of rejection.
This time, the manipulation did indeed take place. in vivo, in a brain-dead patient and after obtaining consent from their family. UOnce the transplant was performed, the kidney functioned for two days without any signs of rejection. On the third day, however, a mild immune reaction was observed, but apparently with less damage than in a classic incompatibility, as the authors point out in their study.
This promising, but still experimental, work undoubtedly opens the way to faster transplants with initially incompatible organs which, under the action of chemical treatment, become perfectly transplantable. However, other questions will need to be studied, such as the clinical feasibility of such an experiment or the medium and long-term tolerance of transplanted organs.
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