Closer to getting 'universal' organs for transplant

One of the main barriers to organ transplantation is the need for the

with the recipient's organism.

In this type of intervention, it is essential to take into account the blood group of both patients and the usual 'rules' in transfusions, such as the fact that an individual from

cannot receive blood, tissues or organs from people from

, however, patients with blood from these latter groups can benefit from donations from people with group 0, often called

A mistake in this compatibility can produce a hyperacute rejection of the donated organ and put the recipient's life at risk, so these barriers are rigorously controlled.

However, research by a group of Canadian scientists could soon put an end to this stumbling block, making it possible to create 'universal' organs for transplantation that do not need to take blood group into account.

The details of his work are published in the journal

.

According to their data, using a

, it is possible to convert a group A organ into a group 0 organ, which would be suitable for transplantation in any patient.

The researchers, led by scientists from the Ajmera Transplant Center in Toronto (Canada), have demonstrated this in preclinical experiments with lungs, but the proof of concept could be extended to other organs.

Blood groups are determined by the presence of antigens on the surface of red blood cells.

Thus, if a person has a group A, this means that their red blood cells present on their outer membrane 'distinctives' (antigens) of type A. These antigens, which are also present in the blood vessels that supply the organs, can trigger a

if the body does not recognize them as its own.

For example, an individual with group 0 does not have A, B or AB antigens in his body;

therefore, your body recognizes them as foreign and attacks them if it comes into contact with them.

To break these barriers, the scientists designed an enzyme cocktail (a combination of FpGalNAc deacetylase and FpGalactosaminidase) and first successfully tested its effectiveness on blood cells and three human aortic artery samples.

Then, using an ex vivo perfusion platform, they tested the method on human lungs that had been ruled out for transplant.

Ex vivo perfusion is commonly used to condition organs and keep them at a suitable temperature before transplantation, but this time, it was also used to infuse the enzyme combination.

To check the effectiveness of the technique, another lung was used as a control.

The scientists verified that the cocktail had been able to

in a period of four hours.

And through an experiment that mimicked the conditions of an incompatible transplant, the scientists were able to verify that the treated lungs showed no signs of rejection.

Scientists are very optimistic about the achievement and hope to start a

"It is still a preclinical experience, we do not know if these transplanted lungs would have the same behavior, but it does seem that lungs could potentially be transformed with this approach and I understand that other types of organs from group A to group 0", explains Beatriz Domínguez- Gil, director of the National Transplant Organization (ONT).

"If we could potentially generate lungs or organs in which the blood group no longer had that relevance, we would increase the chances of transplantation, particularly for patients who have more difficulties," adds Domínguez-Gil, who recalls that because they can only receive donations from people with the same blood group, "usually group 0 recipients are those who have greater difficulty in transplanting or take longer to transplant".

To prevent people with these characteristics from being penalized in accessing a transplant, in Spain the allocation criteria establish that, with few exceptions, group 0 organs are used in group 0 recipients. But, in general, in all the world, these patients take longer than the rest to receive a transplant.

According to data from the ONT, regarding the

, in 2021 50% of patients of any blood group were transplanted in 4 months.

Those in group 0 took a median of 123 days, while group B, 109 and group A, 92.

Although the approach proposed by the Canadian researchers is innovative, Domínguez-Gil recalls that there is

.

"In Spain, with different approaches, incompatible AB0 transplants have been performed in the kidney and liver and there have been several cases of infant heart transplantation".

"What is done is to use a desensitization strategy in the recipient. The recipient is treated to prevent this hyperacute rejection phenomenon from occurring due to blood group incompatibility. Good results have been achieved, but it is true that the burden of immunosuppression and the treatment that you have to do to the recipient can generate more complications than an AB0 compatible transplant," says Domínguez-Gil.

In the case of children, relatively recently, an AB0-incompatible heart transplant program was launched for children up to 14 months of age using techniques that take advantage of their immature immune system to prevent rejection.

"In these cases, the strategy goes through the treatment of the recipient."

With this new approach, instead, what is transformed is the organ.

"What they propose in this work is just the opposite idea: converting the organ into a

In this way, more transplant options are achieved for patients on the waiting list," says Alberto Jáuregui, head of the Thoracic Surgery Service and Lung Transplant at the Vall d'Hebron Hospital in Barcelona.

This expert, who will soon start an AB0-incompatible transplant program similar to the one already done in pediatric heart transplantation, is not surprised that this advance comes from the Toronto group.

Although the first lung transplant performed on a human was in 1963 by the team of American surgeon

, the graft worked only a few days.

After that experience, there were some more attempts in different parts of the world, however, the lack of development of immunosuppression did not allow the implementation of this technique until well into the 1980s. Then, a team from Toronto General Hospital published in 'The New England Journal of Medicine' his experience with two patients who received the transplant successfully;

the patients had not only survived surgery, but had long-term follow-up.

Since then, this Canadian center

. "

Among the contributions of the Toronto group to the advancement of this type of graft, is the development of the

perfusion technique to preserve the lung outside the body.

"Originally devised by the Swedish scientist Stig Steen, in Toronto it was taken to another dimension, so that in addition to keeping them outside the body, it repairs the lungs in a state that

would not be considered for transplantation."

Both Domínguez-Gil and Jáuregui, who was in charge of the team that carried out the first lung transplant in Spain on a patient with Covid-19, and who recently also performed a third double-

on the same patient, consider that We still have to wait for the clinical development of this advance.

It will take a few years of research, and the safety of all steps confirmed, before it can be safely used on patients.

"We have to see what happens in the long term with the people who are transplanted with this technique, and this will take time, but it is a brave step that in the future can help reduce the waiting list."

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