October 10, 2024, Xenotransplantation
Greetings, Kidney Friends!
Kidney transplantation is the most effective treatment for end-stage renal disease, saving the lives of patients with kidney failure, but the shortage of kidneys remains the most critical challenge. Consequently, xenogeneic organ sources, particularly pig-derived organs, are viewed as a potential solution to the shortage of transplantable organs in the future.
Both preclinical and early clinical studies of pig kidney transplantation are progressing rapidly. Scientists have conducted pig kidney transplants and found that the transplanted kidneys initially excrete toxins normally but often lose function rapidly, falling short of meeting clinical kidney transplantation standards.
What Causes This Outcome?
Currently, scientists attribute the primary reason to rejection. Simply put, pig genes are significantly different from human genes. When a pig kidney is transplanted into a human, the human immune system recognizes it as foreign, attacks the transplanted kidney, and ultimately rejects it.
Is There a Solution to This Problem?
Based on current research, the likely solution involves genetic modification, or gene editing, of pigs. Through gene editing, pig kidneys can be modified to appear more like human kidneys to the human immune system by altering their easily targeted sites, thereby protecting pig kidneys transplanted into humans.
Research Progress on Gene-Edited Pigs in China
Currently, China has conducted extensive preclinical research on gene-edited pigs. Since 2020, numerous teams in China, including Academician Dou Kefeng’s team at Xijing Hospital, the Sun Shengkun team at the 301 Military Hospital, the Chen Gang team at Wuhan Tongji Hospital, and the Wang Yi team at Hainan No. 2 Hospital, have successfully performed gene-edited pig-to-monkey kidney transplants (using monkeys as recipients instead of humans for research purposes). In the short term, these pig kidneys exhibited some degree of kidney function in monkeys, but long-term outcomes remain unreported. Meanwhile, international scientists have extended the kidney graft survival time in pig-to-monkey kidney transplants to an impressive more than 2 years.
In March, gene-edited pig kidney transplants garnered two major headlines. In March, Dou Kefeng’s team at Xijing Hospital conducted liver and kidney transplants from transgenic pigs into brain-dead patients, marking China’s first preclinical pig-to-human kidney transplantation study of 2024. Globally, five pig-to-human kidney transplants have been conducted, all in brain-dead patients. As of April 18, the transplanted kidney had functioned normally for 20 days. For the study, they used six gene-edited pigs, genetically modifying six genes by deleting three pig genes and introducing three human genes. On March 16, Massachusetts General Hospital in the U.S. reported the world’s first case of transplanting a gene-edited pig kidney into a living person, shortly after Dou’s report. The pigs they used had three genes removed (similar to Dou’s team), seven genes added (to produce a human protein that prevents organ rejection), and 59 additional genes modified (to prevent swine virus infection). The pig kidney functioned normally in the patient, who was discharged on April 3 and passed away nearly two months later.
Currently, with robust support from Fudan University, our hospital’s kidney transplantation team is enhancing the xenotransplantation research platform and plans to progressively conduct xenotransplantation studies on gene-edited pigs, collaborating with domestic and international scientists to contribute to kidney xenotransplantation research.
That concludes today’s discussion. If you find this article helpful, please follow, like, save, share it with friends, or learn more about kidney transplantation. Until next time.
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