Scientists have taken a step closer to creating public transplant organs

Scientists have successfully transformed donated lungs into public transplants in an experimental conceptual test. This means that, in theory, the lungs should be able to be transplanted into the body of any recipient, regardless of their blood type (as long as the transplanted organ is the right size).

In a new study published Feb. 16 in the journal Science Translational Medicine, researchers performed experiments on general lungs in an extrapulmonary perfusion (EVLP) device that keeps lungs alive outside the body. According to Dr. Marcelo SaipelA professor of surgery at the University of Toronto and lead author of the study, the authors of the study plan to test such organs in a clinical trial with human receptors in the next year and a half.

the doctor Richard Ann. PearsonHarvard Medical School, a professor of surgery, said the technology could help reduce the number of donated lungs that have to be discarded because they do not match the size and blood type of nearby receptors. Transplanted organ size and blood type are the primary factors used to match organ donor and recipient.

In addition, according to Dr. Pearson, this achievement should help address the problem of blood type O lung deficiency in patients with blood type O. The waiting time of this group of patients is the longest and the shortage of these organs is the most severe. The risk of dying while waiting for a lung transplant in patients with blood type O is 20% higher than in patients with other blood groups. They have to wait longer; Because they can not get a transplanted organ from other blood groups.

Donated lungs

Scientists have developed a new technique that turns donated lungs into public transplant organs that can be transplanted into the body of people of any blood type.

From blood type A to blood type O.

Each person’s blood type refers to whether certain sugar molecules Antigen They are called, whether they are on the surface of red blood cells or on the surface of blood vessels inside their body. These antigens are known as A and B antigens. People with blood type A have only A antigens and people with blood type B have only B antigens. People with blood type AB have both, and people with blood type O do not have either of these antigens.

While red blood cells and blood vessels carry these antigens, plasma (the fluid and transparent part of the blood) contains antibodies that react to certain blood antigens. For example, people with blood type A have anti-B antibodies in their plasma; Therefore, if the blood of a person with blood type B is transferred to a person with blood type A, his immune system sees this blood as an external agent and attacks it quickly.

Similarly, people with blood type O have anti-A and anti-B antibodies in their plasma; Thus, their immune systems attack red blood cells and organs that contain antigens A or B (or both). Therefore, organ recipients who have blood type O can only receive organ donors who have blood type O and do not have any of these antigens.

Because individual organs with blood type O do not have antigens, they can be attached to any receptor in any blood type. Due to the high demand for such transplant recipients, people with blood type O spend the most time on the transplant waiting list.

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Saipel is trying to fix this problem Stephen Withers, Professor of Biochemistry at the University of British Columbia, applied for cooperation. Withers’ lab was working on a way to separate antigens from red blood cells A, B, and AB to actually convert these cells to the general blood type O. In 2018, the team discovered a group of enzymes in the human gut that can do this very efficiently. The two groups also collaborated with researchers at the University of Alberta to conduct a new study.

In a new study, researchers placed lungs donated from people with blood type A under two enzymes called FpGalNAc deacetylase and epipalactic galactosaminidase (the lungs used in the study were not suitable for transplantation into patients). The lungs received enzymatic treatment with EVLP support. The device kept the lungs at normal body temperature and pumped a solution of nutrients, proteins and oxygen into the lungs.

Using the enzyme for four hours, the researchers were able to remove 97% of A antigens from the lungs. When Saipel et al. Use the EVLP machine for lung transplantation, they usually leave the organs in the machine for about four to five hours; Therefore, according to him, this method is clinically possible.

The research team also performed an immunoassay using three pairs of blood type A lungs. They treated the right lungs with enzymes and did not enzymatically treat the left lungs. After the lungs were in EVLP for four hours, they injected type O plasma into the organs, which contained anti-A and anti-B antibodies, and examined the condition of the different lungs.

The researchers specifically looked for any signs of rejection of the superacute graft, in which the antibodies attach rapidly to the organ, causing extensive damage and disrupting its function. Saipel said:

Enzyme-treated lungs functioned quite well; Untreated lungs, on the other hand, quickly showed signs of super-acute graft rejection.

Saipel et al. Are currently preparing a proposal for a clinical trial of enzyme-treated lungs. In human patients, the team can address questions that cannot be answered in a laboratory study.

For example, at some point after the transplant, the treated lung cells are likely to start producing blood antigens again, Saipel said; Because the transplant organ produces new cells. At that point, will the immune system suddenly attack the transplanted organ? “We do not think that will happen because of a phenomenon called adaptation,” he said.

If in the first few days after transplantation, an organ can avoid rejection of the subacute transplant, it can adapt or resist future attacks on the recipient’s immune system. Saipel said this has been shown to be a kidney transplant between people with incompatible blood types.

According to UCLA Health, these incompatible transplants can be successful if they are removed in the bloodstream antibody procedures just before the transplant. According to Saipel, the antibodies come back later; But they do not harm all donations; Although the exact cause is somewhat unknown. He said they would look for signs of the phenomenon happening in his clinical trial.

According to Pearson, human trials should show that the enzymes used to separate blood antigens do not harm patients; Because the recipient is likely to be exposed to small amounts of them. “Based on its mechanism of action, I do not expect it to be a significant issue,” he said. Pearson added that this enzyme therapy could eventually be useful in addition to the lungs, other transplant organs, and blood groups used for blood transfusions. “There is no reason why it should not be used for cell or other solid organ transplants,” he said.

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