The first successful transplantation of multi gene edited pig kidney into human body in China

2024-04-08

"As of April 7th, the transplanted kidney has been working continuously for 13 days and is functioning well in the recipient's body, producing urine normally," Qin Weijun, director of the Department of Urology at Xijing Hospital of the Air Force Military Medical University, told reporters. On March 25th, the Qin Weijun team performed a multi gene edited pig brain death recipient xenograft kidney transplantation surgery, transplanting the kidney of a multi gene edited pig into the body of a brain death recipient. This is another major breakthrough in the field of xenotransplantation research made by the hospital after the world's first successful "multi gene edited pig brain death recipient" xenograft liver transplantation on March 10th. Kidney transplantation is currently the only means to cure end-stage kidney disease. However, organ shortage has become a global challenge in the field of transplantation. There are over one million end-stage renal disease patients in China, and only over 10000 cases of allograft kidney transplantation are performed annually. In recent years, with the deepening development of gene editing technology and immunology, xenotransplantation research is expected to become a new way to solve organ shortages. Among them, a series of significant breakthroughs have been made in the research of gene edited pig kidney transplantation. Six cases of multi gene edited pig brain death recipient xenograft kidney transplantation have been carried out abroad, as well as one case of gene edited pig human xenograft kidney transplantation surgery. Since 2020, the Department of Urology at Xijing Hospital has participated in multiple studies on gene edited pig monkey kidney transplantation and combined liver kidney transplantation. Building on previous research, the team conducted an innovative exploration using multi gene edited pigs as donors and brain death recipients as recipients. It is reported that the donor pig for this surgery was provided by Chengdu Zhongke Aoge Biotechnology Co., Ltd. Three genes that can cause hyperacute rejection were knocked out, and one complement regulatory protein gene and one coagulation regulatory protein gene were transferred. After three evaluations by the hospital, the transplant recipient was determined to have brain death, and their family members agreed to participate in this xenograft kidney transplant study free of charge. Under the guidance of Dou Kefeng, an academician of the CAS Member, a professor of Xijing Hospital, and Tao Kaishan, director of hepatobiliary surgery, 21 departments worked together, and Qin Weijun's team performed the operation. No hyperacute rejection reaction was observed during surgery. During this period, the research team fully observed the working status, various indicators, and processes of xenograft kidneys in the human body, and further explored the mechanisms of immune rejection, coagulation disorders, and pathogenic infections in xenograft kidneys. When it comes to why pig kidneys were chosen as transplant donors, Qin Weijun explained, "Pigs are similar to humans in terms of genetic relationships and levels, and the genetic differences between different species are relatively small. Moreover, their organ sizes and physiological functions are similar to those of human organs, which theoretically can replace human organs to function." Qin Weijun introduced that gene editing of pig cells is a relatively mature technology, and pigs have strong reproductive ability and are easy to scale up, making them the best choice for xenograft donors under current technological conditions. In response to the issue of rejection, Qin Weijun stated that the most important transgenic technology currently is CRISPR/Cas9 technology. The team reduces the occurrence of xenograft rejection through knockout/transfer strategies. Qin Weijun believes that this surgery is an important step for China to move towards the forefront of xenograft kidney transplantation, and will provide clinical research and support for xenograft kidney transplantation

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