Recently, a collaborative team led by Academician Jiahong Dong from Beijing Tsinghua Changgung Hospital, along with Zhong Zeng's team from The First Affiliated Hospital of Kunming Medical University and Hongjiang Wei 's team from Yunnan Agricultural University, successfully transplanted the liver and kidney from an 8-gene edited pig into a brain-dead human patient. This groundbreaking procedure is the first of its kind in the world.This research successfully demonstrated the feasibility of using gene-edited pig organs in combined human organ transplantation, laying a crucial foundation for further studies and improvements in xenotransplantation technology.
The gene-edited pig’s kidney and liver were planned to be transplanted into a brain-dead recipient. A multidisciplinary team comprising dozens of experts from the departments of organ transplantation, anesthesia, surgery, and intensive care at Beijing Tsinghua Changgung Hospital and The First Affiliated Hospital of Kunming Medical University collaborated on this challenging surgery, which was completed in 8.5 hours.
The donor pig used in this transplant was genetically modified by Wei Hongjiang’s team using gene editing and somatic cell nuclear transfer technology. Eight genes were edited: three pig xenogeneic sugar antigen synthesis genes (GGTA1, CMHA, β4GalNT2) were knocked out to eliminate hyperacute rejection, three human complement regulatory proteins (hCD46, hCD55, hCD59) were introduced to mitigate acute rejection caused by the human complement system, and two regulatory proteins (hTBM, hCD39) were added to prevent coagulation disorders and subsequent rejection.
After the donor pig was anesthetized, the organ retrieval team first removed the liver and kidney as a whole and selected the left kidney for transplantation. They performed an ectopic kidney transplant first, and once the circulation was restored, the transplanted kidney turned bright red and urine began to flow from its ureter.
Next, they completed the auxiliary orthotopic partial liver transplant by removing the recipient’s left liver lobe and transplanting the donor pig’s left outer lobe of the liver. After the transplanted liver was revascularized, bile was observed flowing from the bile duct. Post-operative ultrasound confirmed good blood flow in both the transplanted liver and kidney.
Zhong Zeng explained that this xenotransplantation, utilizing ectopic kidney transplantation and auxiliary orthotopic partial liver transplantation, is an innovative application based on previous research on “gene-edited pig-monkey” xenotransplantation. Both the liver and kidney were functional post-transplant. Before the study ended, the transplanted kidney functioned for over seven days, and the harvested pig kidney showed good texture and normal color after the study concluded.
Hongjiang Wei stated that gene editing allows scientists to modify pig genes to improve compatibility with human bodies, reducing rejection reactions. Currently, the use of multi-gene edited pigs as xenogeneic organ donors is under extensive research and validation.
Jiahong Dong highlighted that organ transplantation is the most effective treatment for patients with end-stage organ failure. However, the severe shortage of donor organs is a major bottleneck in the development of organ transplantation. In China, approximately 300,000 patients with end-stage organ failure are waiting for transplants each year, but only about 20,000 can receive them. Xenotransplantation is seen as a promising solution to this problem in the future.
Currently, international research on xenogeneic liver transplantation is still in its exploratory phase, and gene-edited animal organs cannot fully replace human organs. How to advance xenogeneic liver transplantation to clinical application remains a major scientific challenge for clinical physicians and medical scientists.
The data obtained from this “gene-edited pig-human” combined liver and kidney xenotransplantation study preliminarily confirmed the unique interactions between xenogeneic gene-edited organs and the human immune system, as well as the specificity of different xenogeneic organs in terms of gene expression patterns and immune responses in the human environment. This research will play a crucial role in improving gene editing protocols, advancing basic research in transplant immunology, and exploring the development of xenotransplantation technology.
