Incremental Progress Towards Xenotransplantation

In between today and a future in which cell therapies are advanced enough to repair organs in situ a range of sophisticated transplant treatments will emerge to address organ failure. Among the present contenders are decellularization of donor organs, artificial organs of various types, including bioprinted tissues, and xenotransplantation, the use of animal organs. The latter is moving towards practicality, step by step:

[Researchers] have successfully transplanted hearts from genetically engineered piglets into baboons' abdomens and had the hearts survive for more than one year, twice as long as previously reported. This was achieved by using genetically engineered porcine donors and a more focused immunosuppression regimen in the baboon recipients. "Until we learn to grow organs via tissue engineering, which is unlikely in the near future, xenotransplantation seems to be a valid approach to supplement human organ availability. Despite many setbacks over the years, recent genetic and immunologic advancements have helped revitalized progress in the xenotransplantation field."

[Reseachers] developed techniques on two fronts to overcome some of the roadblocks that previously hindered successful xenotransplantation. The first advance was the ability to produce genetically engineered pigs as a source of donor organs. The pigs had the genes that cause adverse immunologic reactions in humans "knocked out" and human genes that make the organ more compatible with human physiology were inserted. The second advance was the use of target-specific immunosuppression, which limits rejection of the transplanted organ rather than the usual generalized immunosuppression, which is more toxic.

In this study, researchers compared the survival of hearts from genetically engineered piglets that were organized into different experimental groups based on the genetic modifications introduced. The gene that synthesizes the enzyme alpha 1-3 galactosidase transferase was "knocked out" in all piglets, thus eliminating one immunologic rejection target. The pig hearts also expressed one or two human transgenes to prevent blood from clotting. This longest-surviving group was the only one that had the human thrombomodulin gene added to the pigs' genome. Thrombomodulin expression helps avoid some of the microvascular clotting problems that were previously associated with organ transplantation.



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