China Achieves World's First Liver Xenotransplant Using Domestically Developed Gene-Edited Pigs

On March 14, 2024, Xijing Hospital of the Air Force Medical University announced a major breakthrough in clinical research on xenotransplantation.Academician Dou Kefeng, Director Tao KaishanLed the team to successfully perform an auxiliary whole-liver transplantation from a multi-gene-edited pig into a brain-dead patient,First Exploration of the Feasibility of "Gene-Edited Pig-to-Human" Liver Xenotransplantation.

In this procedure, the transplanted gene-edited pig liver began secreting bile immediately upon reperfusion, with no signs of hyperacute rejection observed, and has remained functional for over 96 hours.It is reported that this xenotransplantation of a gene-edited pig liver into a human is the first case of its kind worldwide.

Academician Dou Kefeng and Director Tao Kaishan performed the surgery (Image source: Xijing Hospital, Air Force Medical University)

Organ transplantation is the most effective treatment for end-stage organ failure, but there is a severe global shortage of donor organs, with patients dying every day while on waiting lists. To address this critical clinical challenge, researchers have begun exploring xenotransplantation,can be trapped inImmunological Rejection and Biosafety Risks...and other issues, this field has consistently struggled to achieve breakthrough progress.

As early as17th CenturyIn Western Europe, physicians attempted to save patients with uremia by using sheep kidneys, but these efforts ended in patient death. Subsequently, there were continuous attempts by doctors to perform xenotransplantation using organs from animals such as chimpanzees; however, due to uncertain efficacy and a series of medical ethical issues, these practices were ultimately halted.

By the end of 2021, two teams of physicians in the United States had successively completed three cases of transplanting genetically edited pig kidneys into brain-dead human bodies, spurring a series of“Preclinical Research Models for Xenotransplantation”With its advent, allogeneic transplantation has once again returned to the public spotlight.

On January 7, 2022, a team led by Bartley Griffith at the University of Maryland Medical Center transplanted a genetically modified pig heart into a patient.Completed the world's first pig-to-human heart transplant, extending the patient's life by two months, which is undoubtedly a significant success and a milestone event in the field of xenotransplantation.

By 2023, a team led by Robert Montgomery at NYU Langone Health transplanted pig hearts with 10 gene edits into two brain-dead human patients, monitoring xenograft cardiac function, hemodynamics, and systemic responses over a 66-hour period. The results showed that both xenografted hearts exhibited robust cardiac function immediately after transplantation, with no evidence of rejection or zoonotic disease transmission.

Therefore,The team believes that pig-to-human cardiac xenotransplantation can be successfully performed without hyperacute rejection or zoonotic disease transmission.

It is worth noting that both the U.S.-based Bartley team and Academician Dou Kefeng’s team choseGene-Edited PigsAs an organ donor for allogeneic transplantation, this also appears to have become the consensus in current clinical research on xenotransplantation.

First, pigs reproduce rapidly and are extensively farmed for food, resulting in fewer ethical concerns. Most critically, pig organs are similar in size to human organs, yielding transplantation outcomes far superior to those from other animals. Consequently, pigs have become an ideal source for human organ transplantation, spurring the rise of the “gene-edited pig” market.

Currently, multiple companies in China have established a presence in the field of xenotransplantation. The donor pig used by Academician Dou Kefeng’s team in this procedure was sourced from a domestic Chinese enterprise.Zhongke Aoge。

Through collaborations with research institutions and universities, Zhongke Aoge has achieved multiple breakthroughs in the development and application of gene-edited miniature pig models. As of 2022, the company’s “gene-edited pigs” comprised ten major strains, three of which are suitable as donors for kidney transplantation.

In addition to breeding xenotransplantation donor pigs, Zhongke Aoge has also leveraged its patented gene-editing technologies to launch a range of products—including medical-grade porcine biomaterials, low-immunogenicity biomaterials, and gene-editing and cloning services—thereby providing support for xenotransplantation research.

Below the top tier, China is also home to several other mainstream companies, including Geland Biotech, Saino Bio, and Zhenzhi Medical.

Gailand BioThe cultivated “gene-edited pigs” can serve as donors for xenotransplantation of organs such as corneas, skin, bioartificial livers, kidneys, and hearts, with corneal donors being a major specialty of this company. In 2021, Gailand Biotech’sCorneal Endothelial Tissue GraftEthical approval for clinical research has been obtained. Meanwhile, xenogeneic bioactive skin has demonstrated successful outcomes in a pig-to-rhesus monkey skin transplantation model and will be submitted for regulatory approval as a medical device product in the future.

Sino BiologicalFocusing primarily on the research, development, and manufacturing of xenogeneic cell transplantation products, we have successfully bred two lines of “gene-edited pigs.” One is exclusively dedicated toIslet Cell Transplantation, while the other can provideIslet Cell TransplantationofHumanized GeneAmong them, the “gene-edited pigs” specifically bred for islet cell transplantation have met the DPF standard testing requirements and are available for preclinical and clinical studies in xenotransplantation.

Additionally,Zhenzhi MedicalMost of its R&D pipeline is focused on drug development using synthetic biology technologies, though it has also achieved modest success in its tissue and organ regeneration pipeline. According to reports from UK media outlets such as the Daily Mail and US publications like New Scientist, in late 2020, researchers from Zhenzhi Medical, the Shenzhen Institutes of Advanced Technology of the Chinese Academy of Sciences, the First Affiliated Hospital of Nanchang University, and other institutions jointly developed a gene-edited pig and successfully completed skin transplantation experiments in cynomolgus monkeys.

Nowadays, xenotransplantation has witnessed breakthrough advancements in both donor sources and surgical techniques; however, numerous technical challenges and safety risks remain to be addressed. Following the success of Academician Dou Kefeng’s team, more researchers are expected to engage in this field. Although the road ahead is long, we must proceed with optimism.