A genetically modified porcine liver has been successfully transplanted into a human subject, constituting a historic precedent in the field of organ transplantation. The liver demonstrated functional viability for a period of 10 days within the body of a brain-dead patient, without eliciting signs of immune rejection.
Procedure Designed as Proof of Concept
The experimental procedure was conducted by a multidisciplinary medical team from the Fourth Military Medical University in China, under the supervision of Kai-Shan Tao, Zhao-Xu Yang, Xuan Zhang, and Hong-Tao Zhang. The intervention was executed in a brain-dead human subject, whose native liver was preserved in situ.
The porcine liver was not intended as a full replacement but was instead positioned within the abdominal cavity as an auxiliary graft, connected to the patient’s circulatory system to enable physiological monitoring.
This auxiliary design was selected to facilitate close observation of the graft’s integration without compromising the host’s native hepatic functions. The primary objective was to evaluate the porcine liver’s metabolic activity and immunological compatibility under clinical conditions.
Six Genetic Modifications Mitigate Immune Rejection
The transplanted liver was sourced from a genetically engineered pig, developed with six targeted genetic modifications. These included the removal of endogenous genes responsible for hyperacute rejection—a rapid and destructive immune response—and the insertion of specific human genes designed to enhance histocompatibility.
These modifications were strategically implemented to suppress xenoantigen expression and promote tolerogenic interaction with the human immune system. The immunosuppressive regimen applied during the study further inhibited T-cell and B-cell activation, mechanisms primarily responsible for organ rejection in xenogeneic contexts.
Porcine Liver Demonstrated Essential Functional Outputs
Throughout the 10-day observation window, the porcine liver exhibited sustained functional activity. Key hepatic functions were confirmed via the secretion of bile and synthesis of porcine albumin, both serving as fundamental indicators of baseline hepatic performance.
The surgical team also reported stable hemodynamic parameters and adequate hepatic perfusion velocity, suggesting the graft maintained sufficient vascular integration.
The study concluded on the tenth day at the request of the patient’s family, not due to medical complications. By that time, the graft remained fully functional and free from observable immune-mediated damage.
Because the host’s native liver remained functional during the study, the clinical team acknowledges that it is not yet possible to determine whether the porcine graft alone could support an individual experiencing hepatic failure.
Nonetheless, the absence of immune rejection and the presence of stable metabolic function propose a viable intermediate solution for patients awaiting human liver transplantation.
Broader Implications for Xenotransplantation
This initiative builds upon prior advances in the domain of xenotransplantation. In 2023, a modified pig liver was externally connected to a human subject for 72 hours. Likewise, genetically modified porcine kidneys have previously been transplanted into brain-dead patients with promising outcomes.
However, because hepatic function encompasses more complex regulatory and metabolic pathways compared to renal activity, successful liver xenotransplantation was previously considered a more formidable challenge.
This study demonstrates that with precise genetic engineering and immunosuppressive strategies, even the sophisticated functional profile of the liver can be preserved in a xenogeneic context.
Expert Assessment and Future Research Directions
Independent experts have acknowledged the significance of the findings. Rafael Matesanz, nephrologist at the National Transplant Organization in Spain, stated that the experiment “opens up a different path” toward the temporary replacement of diseased livers using xenogeneic organs until human grafts become available.
Similarly, Iván Fernández Vega, neuropathologist at the University of Oviedo, commended the methodological rigor of the study, highlighting the “exhaustive clinical, immunological, histological and hemodynamic characterization” as setting a new standard in the field.
Despite these advances, the study’s scope was limited to a single subject and a narrow subset of liver functions—primarily bile production and albumin synthesis. Comprehensive functional assessments and larger sample sizes will be necessary to evaluate full therapeutic applicability.
Toward Clinical Integration of Xenogeneic Organs
This research, now published in Nature, represents a foundational advancement in the integration of genetically modified animal organs into human clinical frameworks.
The findings suggest that porcine organs, appropriately modified, could be deployed as temporary or even transitional support mechanisms for critically ill patients awaiting human donors.
While further investigation is required to establish long-term safety, scalability, and ethical governance, this study affirms the plausibility of xenotransplantation as a meaningful extension of contemporary transplant medicine.
