Xenotransplantation: pig liver works in living humans for the first time

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A Chinese research team has succeeded in transplanting a genetically modified pig liver into a living cancer patient as a supporting organ (xenotransplantation). The organ was functional for 38 days and took over vital metabolic functions before it had to be removed due to complications.

The procedure, described in the Journal of Hepatology, is a significant advance that builds on earlier experiments and brings xenotransplantation one step closer to clinical application. The 71-year-old patient suffered from advanced liver cancer, and after removal of the tumor, adequate liver function could no longer be guaranteed. The pig liver was therefore used in addition to the patient's own liver to stabilize the patient.

Ten gene modifications to prevent rejection

To prevent immediate rejection, the donor organ was genetically modified on a massive scale. A total of ten modifications were made. “Three xenoantigens […] were switched off to prevent the hyperacute and acute rejection reaction, and seven human genes […] were inserted to improve the regulation of complement activation, blood coagulation, and macrophage phagocytosis,” explains Dr. Konrad Fischer, Head of the Xenotransplantation Section at the Technical University of Munich. This combination of ten gene edits is similar to the procedure used in recent pig kidney transplants in the USA.

The success quickly became apparent: the pig liver produced bile acids and proteins that are important for humans. “The proven production of functional bile acids, blood clotting factors, and complement proteins by the pig liver was particularly remarkable—biochemical processes that were previously considered potentially incompatible with human metabolism,” says Fischer.

Success and setback: the well-known complication occurs

Despite strong immunosuppressive medication, a well-known and feared complication occurred after 38 days: thrombotic microangiopathy (xTMA), in which small blood clots damage the organ. The pig's liver was then removed. Prof. Dr. Uta Dahmen, Head of Experimental Transplant Surgery at Jena University Hospital, explains: “This study is a 'proof of concept' study. However, the researchers did not succeed in preventing the thrombotic microangiopathy (xTMA) that occurred during the procedure.” The patient survived the removal and only died 171 days after the original operation as a result of his cancer.

Classification in the latest developments

Xenotransplantation has made enormous leaps forward in recent years. While it was still considered a distant “organ donation from the stable” in 2019, there have been several transplants of pig kidneys into living patients since the beginning of 2024. Even though the first recipients died after around two months, the medical teams did not attribute this directly to rejection of the organ.

The liver poses a particular challenge. “The main function of the liver is the metabolic component, and the pig liver produces proteins that come from the pig. This poses a greater challenge than the predominantly mechanical component that has to be fulfilled in a heart transplant, for example,” emphasizes Dahmen.

Bridge therapy as a realistic goal

The current case strengthens the hope that xenotransplants can serve as a bridging therapy. “In the future, xenogeneic organs could serve as a short-term, life-saving bridge until the patient's own liver regenerates or a suitable donor liver is available,” summarizes Fischer. The need is immense: according to Dr. Beatriz Domínguez-Gil, Director of the Spanish National Transplant Organization, over 2,300 people died on the waiting list for a liver in Europe alone in 2024.

However, she cautions that the procedures remain experimental: “These cases allow us to glimpse a future in which xenotransplantation is a clinical reality, […] but also highlight the significant obstacles that still need to be overcome.” The current milestone is therefore more than just a technical success; it is a decisive, if not final, step on a long road.

(mack)