January 7, 2022 is a day worth remembering in the history of human organ transplantation - a team of surgeons at the University of Maryland School of Medicine successfully transplanted a genetically modified pig heart into the body of a 57-year-old man with heart failure, David Bennett . This is the world's first transplant of a genetically modified pig heart into a living human.
Organ transplantation is currently the best way to treat end-stage organ failure, but the severe shortage of donor organs is a global medical problem, and xenotransplantation will become the fastest way to solve the shortage of donors.
Dr. Pan Dengke, deputy head of the Xenotransplantation Group of the Organ Transplantation Branch of the Chinese Medical Association and deputy director of the Institute of Organ Transplantation, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, introduced in an interview with reporters that it is not the first time to transplant animal hearts to humans. . In the 1980s, a baboon heart was transplanted to an unfortunate American infant with congenital heart disease, but died within a month of acute immune rejection. This time, the pig heart received by David Bennett has been genetically modified, and there is no hyperacute immune rejection after transplantation. The patient is in good spirits after the operation. It depends on whether the patient can continue to survive in the next few weeks to months.
Pan Dengke introduced that in the past 30 years, with the rise of gene editing and other technologies, great progress has been made in preclinical research on xenotransplantation, and the problems of hyperacute rejection and coagulation disorders in xenotransplantation have been basically overcome through genetic modification technology. At present, the longest survival time of pig organ transplant recipients is 557 days for orthotopic kidney, 195 days for orthotopic heart, and 945 days for ectopic heart. And before the gene-edited pig heart transplant, scientists have completed key tests of the safety and efficacy of gene-edited organs in monkeys.
From October to December 2021, NYU Langone Health Center successfully performed two consecutive trials of gene-edited kidney transplants to brain-dead cases, with no hyperacute rejection, and normal kidney function within 54 hours. This is the first time a gene-edited organ has been tested in humans, and the transplanted kidney is also derived from a gene-edited pig.
According to Pan Dengke, xenotransplantation mainly faces four major problems. The first is immune rejection, the second is coagulation dysfunction, the third is biosafety, and the fourth is ethical controversy. Among them, immune rejection, including hyperacute, acute and cellular immune rejection, is the main problem faced by xenotransplantation. In response to hyperacute immune rejection, gene modification technology has allowed humans to successfully breed cloned pigs with immune-related genes knocked out for the first time, and the development of immunosuppressive agents has greatly promoted the successful application of xenotransplantation.
"Biosafety issues mainly refer to the risk of cross-infection between species. For example, disease transmission, endogenous retrovirus infection, etc., which are also difficult problems that must be solved in xenotransplantation. Pandenke introduced that the biosafety of transplanted organs is a problem. , At present, the barrier environment can be used to purify donor pigs in combination with caesarean section. In addition, gene editing technology can also be used to remove endogenous viruses in pigs.
"Although the research on xenotransplantation has made great progress, the functional compatibility of transplanted organs has become a technical challenge to be solved. Whether the transplanted pig organs can fully utilize the original human organs to maintain hormone secretion and metabolic balance, etc. The function remains to be tested.” Professor Yang Luhan of Harvard University said that solving the risk of xenovirus transmission and immune compatibility of donor pigs is only the “first step in a long march”, and it is still necessary to constantly explore and improve the function of xenotransplanted organs. compatibility.
