Chinese scientists announced the world’s first successful transplantation of a genetically modified pig liver into a brain-dead patient. This represents an important step towards routinely using pig organs to save human lives [1].
Where do we get spare parts?
The shortage of organs for transplantation is a major cause of mortality, but transplantation also plays a role in the broader context of longevity, as it is one of the proposed strategies for radically addressing aging without fully understanding its complexities. Currently, a new organ is transplanted into a patient only when the original organ is failing, but in the future, we might want to proactively “service” our bodies to remain young and fit. However, we must first solve the supply problem.
While growing organs in a lab sounds exciting and might be possible someday, a more practical (albeit less humane) approach involves harvesting organs from one of the most humanlike animals: pigs. However, early attempts to do so had hit the wall of graft rejection. After all, even between humans, finding a good fit is complicated, and transplantations require immunosuppression.
Thankfully, recent advances in genetic engineering have allowed scientists to grow pigs that lack the handful of problematic genes responsible for acute rejection. These pigs also usually have certain human genes inserted to facilitate transplantation. Researchers have transplanted pig hearts and kidneys with relative success before and connected a pig liver to a brain-dead patient for several days. However, until now, no successful pig-to-human liver transplantation had been reported.
A “bridge transplantation”
A paper published in Nature several days ago by scientists from the Fourth Military Medical University in Xi’an, China, describes the first experiment of this kind. The researchers used a liver from a genetically modified Bama miniature pig for heterotopic auxiliary liver transplantation, meaning that the organ was implanted in addition to, and in a different location from, the recipient’s native liver. Specifically, the researchers knocked out the genes GGTA1, CMAH, and B4GALNT2, key mediators of hyperacute rejection, and inserted human transgenes coding for the proteins thrombomodulin, CD46, and CD55.
Although seemingly unusual, this approach mainly serves as a “bridge transplantation,” a temporary measure for patients whose livers have failed while waiting for a suitable human donor. However, this proof of concept lays the groundwork for full-scale transplantations in the future.
After the procedure, the pig’s liver began producing bile and porcine albumin, demonstrating a quick return to function. Liver enzymes were largely normal, aside from a transient spike in AST levels immediately after surgery, potentially originating from tissues other than the liver. The liver “functioned really well” and “smoothly secreted bile,” said study co-author Lin Wang, touting the transplantation as “a great achievement.”
The liver exhibited normal blood flow (hemodynamics) and, importantly, avoided the major coagulation problems encountered in earlier experiments, including the first human cardiac xenotransplantation. The chosen immunosuppression protocol mostly worked well. However, there were also unexpected signs of B-cell activation, which subsided after the immunosuppressant rituximab was used. This suggests that further optimization of immunosuppressive protocols might be needed.
The transplanted liver’s function remained stable for ten days. The experiment’s short duration was a limitation imposed by the patient’s family.
Kidney transplant by the same team
Peter Friend, Professor of Transplantation at the University of Oxford, who was not involved in the study, said: “This is an important study because it advances the field of xenotransplantation from non-human primates to humans, enabling assessment of transgenic xenografts in the context of human immunological and physiological systems.”
While stating that “a very elegant surgical technique” was used, Friend also urged some caution: “The presence of the brain-dead donor’s native liver means that we cannot extrapolate the extent to which this xenograft would have supported a patient in liver failure. However, this study does demonstrate that these genetic modifications allow the liver to avoid hyperacute rejection.”
Another researcher, Iván Fernández Vega, Professor of Pathological Anatomy at the University of Oviedo, Spain, who was also not involved in the study, said: “I found the work very relevant, but we have to be cautious. The quality of the work is very high, both in terms of scientific rigor and the exhaustive clinical, immunological, histological, and hemodynamic characterization of the procedure. It is the first study to demonstrate that a genetically modified porcine liver can survive and exert basic metabolic functions in the human body.”
The team at Xi’an has been working on xenotransplantations for over a decade. Around the same time as the liver transplantation, the researchers also reported one of the world’s first successful pig kidney transplantations. At the time of reporting, the 69-year-old female patient was nearly three weeks post-surgery and reportedly doing well. Pig kidney transplants have so far yielded mixed results: three out of five patients (including the latest one) remain alive, but two others died shortly after their procedures last year.
Literature
[1] Tao, K. S., Yang, Z. X., Zhang, X., Zhang, H. T., Yue, S. Q., Yang, Y. L., … & Dou, K. F. (2025). Gene-modified pig-to-human liver xenotransplantation. Nature, 1-8.
