China makes breakthrough in xenotransplantation with gene-edited pig kidney surviving 184 days in macaque

An organ transplantation research team from Tongji Hospital of Huazhong University of Science and Technology in Wuhan has achieved a major breakthrough, with a gene-edited pig kidney surviving in a macaque for an unprecedented 184 days. This marks the first step toward successful xenotransplantation in China, according to a release by the hospital on Friday.

This success was realized in November, bringing China's xenograft pig kidney transplantation research closer to the international advanced level, and laying a strong foundation for future clinical research, the release said.

Gene-editing pigs to provide organs to humans for performing xenotransplantation remains a key focus area in advanced biotechnology.

China's clinical application technology for organ transplantation is on par with global standards, and the research and development capabilities for gene-edited pigs are steadily aligning with international benchmarks, according to the hospital. 

In the trials involving gene-edited pigs and non-human primates, however, the transplantation of pig kidneys into macaques has faced challenges in achieving long-term survival, which has become a major barrier to advancing xenogeneic kidney transplantation to clinical trials in China, the release noted.

Chen Gang, the team's leading researcher, explained that in xenograft animal testing, 180 days of survival is regarded as the benchmark for achieving long-term survival.

Long-term survival after transplantation of gene-edited pig kidneys in macaques has been reported internationally in nearly 20 cases, and the US has pioneered clinical trials involving pig kidney transplants for patients with uremia, Chen said.

For China to initiate similar clinical case studies, achieving long-term survival in animal experiments remains a prerequisite, Chen added.

Chen and his team have dedicated nearly two decades to xenotransplantation research, focusing specifically on over 20 animal experiments involving kidney transplants from novel gene-edited pigs to macaques in the past five years.

Following continuous refinement and improvements, on May 10, after obtaining ethical approval for animal experiments, they used pCMV-negative four-gene edited pigs (GTKO/β4GalNT2KO/hCD55/hTBM) as donors to transplant a single pig kidney into a macaque, while concurrently removing the macaque's own bilateral kidneys. 

By improving the immunosuppressive regimen, the transplanted kidney achieved a survival period of 184 days, the release noted.

Within five months after the transplantation, the transplanted pig kidney in the macaque functioned entirely normally, and various physiological indicators were largely within normal ranges, according to the release.

Although the transplanted macaque later developed worsening proteinuria over time and experienced chronic rejection mediated by newly formed xenogeneic antibodies, Chen said that they will strengthen measures to suppress antibody production and further improve survival outcomes, laying the groundwork for clinical research.