Pig's heart
Baboons with pig hearts set a new record
A group of American researchers has announced a new record in the field of xenotransplantology (Researchers keep pig hearts alive in baboons for more than 2 years). For more than 10 years, experiments have been conducted in the laboratory of the National Heart, Lung and Blood Institute in Bethesda (USA) on transplantation of pig hearts into the abdominal cavity of baboon monkeys (we have already talked about this earlier). The new publication talks about five monkeys who lived for a long time after such an operation. The longest period was 945 days.
Usually, organ transplantation of another type causes a violent reaction of the immune system. In the first such experiments, animals could live only a few minutes after surgery. When in 2001 scientists obtained genetically modified pigs that had suppressed the activity of the gene responsible for the synthesis of alpha-1,3-galactosyltransferase, one of the enzymes responsible for the rejection reaction of transplanted organs, they managed to ensure that pig organs lived in the body of baboons and other monkeys for months. At the same time, experimental animals had to be given drugs that suppressed the activity of the immune system, which prolonged the life of the transplanted organ, but made the body vulnerable to infections.
The head of the study, Mohammad M. Mohiuddin, and his colleagues tried to select drugs of narrow action that would protect the transplanted organ, but did not disable the entire immune system.
The most promising, in their opinion, was an antibody that blocks communication between certain immune cells by binding to the CD40 receptor on their surface. In the new experiment, the scientists used such anti-CD40 antibodies along with heparin. The hearts were taken from pigs in whose genome the galactosyltransferase gene did not work, but the genes of two human proteins were present. One of them regulated blood clotting, the other blocked signaling molecules that are associated with the immune response.
This combination provided a record survival rate of the donor organ. Then the scientists began to reduce the dose of anti-CD40 antibodies. When these antibodies were not left in the baboons' body, a rejection reaction began. In two baboons who were immunosuppressed for a year, pig hearts could live for some time after lowering the dose of the antibody. In the other two, whose period of suppression of immunity was 100 days, rejection began almost immediately after the dose reduction. In the next series of experiments, scientists intend to test not only the possibility of life of the transplanted heart, but also its ability to perform its functions of pumping blood.
The experimental report is published in Nature Communications (Mohiuddin et al., Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft).
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06.04.2016