Published:2024-11-22 15:33
Human organ transplantation is a key medical technology to save critically ill patients. The biggest obstacle to organ transplantation is the shortage of transplantable organs. Xenotransplantation with pigs as organ donors is bringing a new dawn.
The Asian Organ Transplantation Symposium (TSS) was held in Shanghai on November 22,2008, which was organized by Sun Yat-sen Hospital of Fudan University and officially recognized by the International Transplant Society (TTS) . Domestic and foreign well-known experts on organ transplantation and related disciplines, organ transplantation on the hot and difficult issues in the field of special lectures and discussions.
Zhongshan Hospital affiliated to Fudan University is one of the few comprehensive hospitals qualified for heart, liver, kidney and pancreas transplantation in China, which takes the lead in many technological innovations in the field of organ transplantation. Photo courtesy of Zhongshan Hospital
The shortage of transplantable organs is a worldwide medical problem. Public information shows that China has achieved remarkable results in system design, social mobilization and standard procedures since the launch of the organ donation pilot in 2010, and has achieved double improvements in the quantity and quality of organ donation and transplantation. However, according to the China Organ Transplantation Development Report (2021) , the organ donation rate per million population is 3.73, which is still lagging behind the international advanced level.
More than 100,000 people in the U.S. alone are waiting for organ transplants, according to figures from the U.S. nonprofit organization Organ Sharing Network, Xinhua 2024 reported in April, an average of 17 people die every day while waiting.
China has made remarkable progress in the field of organ transplantation, but it still faces a serious shortage of organs, Zhou Jian, director of Zhongshan Hospital affiliated to Fudan University, said at the seminar. This requires not only further improving the existing organ donation and distribution system to ensure fair, transparent and efficient operation, but also technological innovation.
Zhou believes that, at present, the adoption of advanced medical technology and methods is one of the measures to deal with the shortage of organs. For example, Zhongshan Hospital’s implementation of the world’s first”Abandoned liver” liver transplantation combined with ALPSS surgery and other methods can effectively expand the source of donors and improve the success rate of surgery, thereby alleviating the current tight supply and demand imbalance.
The paper (www.thepaper.cn ) noted that xenotransplantation using pigs as donors was frequently discussed at the conference.
China is a leader in organ medicine, according to John Fung, the current president of the International Society for organ transplantation, who has seen liver transplants performed in Chinese hospitals using Chinese original technology. “There is an impressive amount of medical innovation in China,” he says, noting that the country is also making rapid progress in the field of xenotransplantation.
On March 21, the American 2024 Massachusetts General Hospital announced that a team of surgeons at its transplant center had successfully transplanted a gene-edited pig kidney into a 62-year-old man. This is the first time in the world that a pig kidney has been transplanted into a living recipient. Two months after the operation, the patient died of a heart attack in May.
China, too, soon achieved a breakthrough. In early April, the Xijing Hospital of the Air Force Medical University announced that on March 25 its team had performed a”Multi-gene-edited pig-brain-dead recipient” xenotransplantation of kidney, successfully transplanted a kidney from a multi-gene-edited pig into a brain-dead recipient.
The First Affiliated Hospital of Anhui Medical University announced on May 24 that its team and Yunnan Agricultural University team worked together on May 17, a genetically modified pig liver was successfully transplanted into a 71-year-old man with huge right lobe liver cancer at the first affiliated hospital of Anhui Medical University. This is the world’s first living donor liver xenotransplantation.
The research of Xenotransplantation with pig as donor is rising rapidly.
Zhu Tongyu, vice president of the Fudan University Shanghai Medical College and a professor in the Kidney Transplantation Department of sun yat-sen hospital, told thepaper.cn that the biggest obstacle to organ transplantation is the shortage of organs. Take kidney transplantation as an example, each patient may have to wait 5 to 10 years for a valuable donor. More than 140,000 people have registered for organ transplants in China, but fewer than 20,000 receive them each year, according to 2023 data from the China organ distribution and sharing system, there is a big gap between supply and demand. In recent years, with the promotion of new technologies such as gene editing, great progress has been made in xenotransplantation with pigs as donors.
“Now there is a light at the end of the tunnel,” Zhu said. “There have been several cases worldwide where organs such as kidneys and hearts from pigs have been transplanted into humans and can survive for months.”“Pigs are now recognized around the world as one of the best supplies for humans, and their role is becoming more and more important than in the past,” Zhu said
At the same time, Zhu Tongyu stressed that there are still many problems to be overcome for pigs as organ donors. Pigs and humans are very different. Humans have 23 List of organisms by chromosome count of somatic cells, while pigs have 19. At the same time, zoonosis and immune rejection are challenges in organ transplantation. Further research is needed to keep transplant patients alive for longer.
Since the 1960s, human xenotransplants have been performed on chimpanzees, baboons and other primates, Xinhua reported. However, because of the severe rejection, the survival time of the recipient is very short.
In recent years, pigs have entered the medical field as donors. Because the organ tissue structure, physiological function and size of pigs are similar to human organs, and they are far from human beings, zoonotic diseases are less, therefore, it is regarded as one of the ideal donors for human xenotransplantation. Scientists used gene editing to“Knock out” genes that could cause rejection in pigs and insert human genes to improve the long-term survival of recipients. Currently, the protocol of multi-gene-edited pigs as XENOGENEIC organ donors is being extensively investigated and validated.
For example, 2024 in May, academician Dong Jiahong’s team from Tsinghua University (Beijing) , Kunming Medical University Medical University (Beijing) , and Yunnan Agricultural University Wei Hongjiang’s team successfully transferred the liver and kidney of an 8-gene-edited pig, and transplanted into a brain-dead patient.
At that time, scientists carried out 8 gene editing on donor pigs through gene editing technology and somatic cell nuclear transfer technology, and knocked out three porcine heterologous sugar antigen synthesis genes (GGTA1, CMHA, β4galnt2) , respectively, in order to eliminate hyperacute rejection, three human complement regulatory proteins (HCD46, HCD55, HCD59) were transferred, which can effectively alleviate the acute rejection caused by the activation of the human complement system. At the same time, the regulatory proteins that inhibit coagulation (HTBM, HCD39) were transferred, can effectively avoid the rejection caused by coagulation disorders.
In the research of organ transplantation, apart from the problem of organ source, Zhou Jian and other experts also talked about the hidden dangers of immunosuppression faced by transplant patients. Usually, transplant patients must be kept on immunosuppressants to prevent rejection, but this also weakens their resistance to outside pathogens, making them more susceptible to infection. How to improve the immunity of patients after transplantation and reduce the risk of infection is an urgent problem.
To address this issue, Zhu’s team first proposed an“Innovative model for the diagnosis and treatment of severe and specific infections in organ transplantation.”. This model includes the development of new diagnostic systems to accurately diagnose pathogens, the use of phages to treat refractory bacterial infections after transplantation, and the development of BK virus vaccines to prevent viral infections. This series of measures can effectively improve the ability of patients to fight infection.
Since 2018, Zhu’s team has launched the first clinical trial of phage therapy in China, achieving a clinical improvement rate of 78.3% . During this period, the team published the first case report of phage therapy in China, as well as the world’s first case set and case paper on phage therapy for covid-19 secondary bacterial infection. In 2022, Zhu Tongyu’s team initiated the establishment of the Chinese Phage Research Alliance, and released the expert consensus and group standards for phage therapy and phage preparation quality standards. “With the advancement of this research, patients will live longer and have a higher quality of life after organ transplantation in the future.” Zhu said phage therapy could be used to prevent, diagnose and treat superbug infections, in the field of organ transplantation has great application space.
