To create a "replacement" of human organs, functional compatibility is still a problem

Over 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

——Pan Dengke, deputy head of the Xenotransplantation Group of the Chinese Medical Association Organ Transplantation Branch, and deputy director of the Institute of Organ Transplantation, Sichuan Provincial People's Hospital

◎Our reporter Wu Chunxin and Luo Chaoshu

Correspondent Wang Xiaoxiao

On January 20, local time, the American Journal of Transplantation published a paper by researchers at Alabama State University, revealing that they successfully completed a trial of transplanting a pair of gene-edited pig kidneys to a brain-dead patient last September.

On January 7, local time in the United States, a surgical team at the University of Maryland School of Medicine successfully transplanted a genetically modified pig heart into a 57-year-old male patient with heart failure

On January 15, according to Professor Wu Zhongjun, director of the Artificial Organ Laboratory at the University of Maryland, the patient has now been separated from the support of extracorporeal membrane oxygenation (artificial lung) and has begun to walk on the ground

Xenotransplantation has been tried many times

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 that human beings have begun to try xenotransplantation a long time ago, in the 1980s.

However, the pig hearts received by the heart failure patients this time have been genetically modified.

Scientists have completed key tests of the safety and efficacy of gene-edited organs transplanted into monkeys ahead of gene-edited pig heart transplants

From October to December last year, NYU Langone Health conducted two successful experiments in which gene-edited pig kidneys were transplanted into brain-dead cases.

In October 2019, a Harvard Medical School Massachusetts General Hospital team successfully used genetically engineered pig skin to cover human burn wounds

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

At present, only the first step of the "Long March" has been taken

Pandenke believes that whether the donor comes from pigs, baboons or others, xenotransplantation must overcome three major problems, namely immune rejection, coagulation dysfunction and biosafety issues

Among them, immune rejection, including hyperacute, acute and cellular immune rejection, is the main problem faced by xenotransplantation

"Biosafety issues mainly refer to the risk of cross-infection between species

In view of the biosafety of transplanted organs, the barrier environment can be used to purify the donor pigs in combination with caesarean section

In 2017, Professor Yang Luhan of Harvard University and her team completed the knockout of porcine endogenous retrovirus-related enzyme genes by using the endogenous gene editing method and gene scissors technology, and successfully cloned the endogenous virus without endogenous virus.

"Although the research on xenotransplantation has made great progress, the functional compatibility of the transplanted organ has become an unsolved problem.

my country's xenotransplantation is gaining momentum

In the field of xenotransplantation, although the leading companies are mainly American companies, Chinese companies are also gaining momentum
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At present, the domestic companies that carry out xenotransplantation research mainly include Sino Biological and Zhongke Oger
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On August 9, 2005, International Online reported that China's first cloned pig was born, and Pandenke participated in the breeding of this cloned pig
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In November 2010, the research team of Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences successfully cultivated 4 genetically modified pigs suitable for human organ transplantation
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Pandenke said that these four pigs are the first organ transplant pigs in China to eliminate the hyperacute immune rejection gene
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In 2018, the Chinese Academy of Agricultural Sciences transferred more than 10 years of scientific research results, the core technology developed for genetically modified pigs and the genetically edited pig population, to Zhongke Oger, transforming laboratory technology into industrial technology
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Pan Dengke introduced that in the research on transplanting gene-edited pig organs into non-human primates, China has adopted the human clinical immunosuppression program and carried out in-depth immune basic research on xenotransplantation
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Currently xenotransplantation is primarily an experimental treatment when no other method is available
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With the rapid development of this field in China, the approval, supervision and ethical system of xenotransplantation all need to be established urgently
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