Chinese scientists have achieved a significant milestone in xenotransplantation, demonstrating that a gene-edited pig kidney can function in a macaque for over six months. This breakthrough, involving a four-gene edited pig kidney transplanted into a macaque, marks a crucial step toward addressing the critical shortage of human organs for transplantation.
The research team, from an affiliated hospital of Tongji Medical College under the Huazhong University of Science and Technology, performed the transplant on May 10. They used pCMV-negative four-gene edited pigs (GTKO/β4GalNT2KO/hCD55/hTBM) as donors, transplanting a single pig kidney into a macaque after removing both of the macaque's native kidneys. The transplanted kidney survived for 184 days, functioning normally for the first five months before signs of chronic rejection appeared.
Chen Gang, the team's leading researcher, noted that in xenograft animal testing, 180 days of survival is regarded as the benchmark for achieving long-term survival. This achievement brings China's xenograft pig kidney transplantation research closer to international standards and lays a strong foundation for future clinical research.
Immunosuppression and Rejection
The researchers employed an improved immunosuppressive regimen to prevent rejection of the foreign organ. While specific details of the regimen were not fully disclosed, common immunosuppressive agents used in xenotransplantation include anti-CD154 antibody, mycophenolate mofetil, anti-thymocyte globulin, tacrolimus, rapamycin, cyclosporine, belatacept, abatacept, sirolimus, fingolimod, and everolimus. Despite these efforts, the macaque eventually developed worsening proteinuria and chronic rejection mediated by newly formed xenogeneic antibodies.
Context of Xenotransplantation
Xenotransplantation, the transplantation of living cells, tissues, or organs from one species to another, holds promise for addressing the severe shortage of human organs available for transplantation. Chronic kidney disease, affecting over 10% of the global population, often leads to dialysis or the need for a kidney transplant. The success of this study provides hope for patients with end-stage organ failure.
Global Efforts in Xenotransplantation
Other research groups have also made strides in xenotransplantation. Scientists at Harvard-affiliated institutions reported a study in 2023 where a kidney from a genetically engineered miniature pig kept a monkey alive for over two years. In 2022, researchers at the University of Alabama at Birmingham transplanted two pig kidneys into a brain-dead human in a proof-of-concept study. Furthermore, in March of the same year, Harvard Medical School physician-scientists transplanted a genetically modified pig kidney into a human with kidney failure, although the recipient lived for only two months.
Future Directions
The Chinese team plans to strengthen measures to suppress antibody production and further improve survival outcomes, laying the groundwork for clinical research. Chen Gang emphasized that achieving long-term survival in animal experiments remains a prerequisite for initiating clinical studies in China. The team is focused on curbing antibody responses to achieve longer graft survival and prepare for human clinical trials.
