Bethesda / Maryland - The combination of new immunosuppression with genetically modified donor animals has extended the survival time of xenotransplants in an animal model to such an extent that the procedure would be interesting for human medicine. However, the publication in Nature Communications (2016; doi: 10.1038 / ncomms11138) still leaves some questions unanswered.
An organ transplant from one species to another triggers an extremely violent "hyperacute" rejection reaction that affects the organ recipient can be fatal within minutes. All attempts to inhibit this rejection reaction with immunosuppressants without making the recipient defenseless against infections have repeatedly failed in recent years. Two developments may now have led to turning point. The first was to change the genome of the donor animals. Because of the comparable size of the organs, pigs in particular come into question here.
Animals are currently the first choice the name "GTKO.hCD46.hTBM", which one has developed. On the one hand, these animals lack the gene for the enzyme alpha-galactosidase transferase (GTKO), which triggers an immune reaction. In addition, the animals were given the human version of "CD46", which is supposed to prevent rejection reactions via the complement system. The third component is the human gene for thrombomodulin (TBM). It is said to inhibit pathological blood clotting.
This alone would not prevent rejection crisis. The second component that is needed for long-term survival is an antibody that inhibits the CD40 receptor on the surface of immune cells and thereby prevents an attack on the transplant. This immunosuppression appears to be associated with acceptable risks for the recipient. According to the report by Muhammad Mohiuddin of the National Heart, Lung, and Blood Institute in Bethesda, Maryland, the baboons that were treated with the CD40 antibody (plus heparin) did not show any noticeable susceptibility to infection.
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The animals that have pig's heart transplanted into the abdominal cavity showed no signs of chronic rejection or organ failure even after two years. The organs would probably have survived longer than 159 to 945 days had the researchers not decided to slowly reduce the immunosuppression. This was done in the hope that in the meantime certain tolerance towards the foreign organs has developed, which, however, was not the case. It appears that immunosuppression must be continued for life even after xenotransplantation.
The researchers want to continue their animal studies in order to optimize immunosuppression. Clinical trials are currently not being considered, and it is not yet clear whether the transplants would develop their full organ function.