Why pigs and not primates? Experts interpret the world's first pig heart human transplant surgery

On January 10, local time, the University of Maryland Medical Center in the United States publicly released news that the center successfully transplanted a gene-edited pig heart into the patient's body through surgery, and after 3 days of transplantation, the heart worked normally and the patient was in good condition.

The gene-edited pig heart transplant was performed by a 57-year-old Resident of Maryland, USA, who had a serious heart attack and was in poor physical condition to receive a human heart transplant or install a pacemaker. As a result, he voluntarily accepted experimental therapies for organ transplantation from different organisms and obtained surgical permission from the US FDA for "compassionate use".

The operation was performed on January 7, local time and was successfully completed. Doctors at the University of Maryland Medical Center said after three days of observation that the transplanted heart produced a pulse and pressure, and the patient was in good condition. It believes that the transplant surgery shows that the hearts of genetically modified animals can function in the human body without being immediately rejected.

According to public information, the pig heart that the doctor transplanted for the patient this time came from a gene-edited pig donor. The donor was edited to knock out 3 segments of genes that could trigger immune rejection and 1 segment of the pig gene that could cause the heart to continue growing, and 6 segments of the human gene were inserted to avoid rejection after transplantation as much as possible.

As of now, the University of Maryland Medical Center has not continued to update the latest status of patients.

Why pigs and not primates?

Back in 1984, a baby with congenital heart disease received a heart transplant from a baboon. But after surviving on a transplanted heart for 21 days, he died.

"Theoretically, primate organoids are more suitable for human transplantation, but being too closely related can also lead to problems such as the virus being more contagious." Sun Hongtao, chief physician of the Department of Cardiac Surgery at Fuwai Hospital of the Chinese Academy of Medical Sciences, said that after exploration, scientists will focus on pigs. The heart structure of pigs is very similar to the human heart, and for the sake of scientific research costs, baboons, orangutans and other primates are not easy to breed, while pig feeding is more common, so pig hearts have been used as training materials for cardiac surgery.

Breeding is relatively convenient, similar to the structure of human organs, and the risk of viral infection is low... Considering various factors, in recent years, pigs have become the main research object of human organ transplant donors. In fact, more than 20 years ago, when Sun Hongtao was still studying for graduate school, there were many research groups that took xenotransplantation as the research direction, but organ transplantation between different species of organisms often occurred within one or two days after surgery.

Allogeneic graft rejection is key

In 2017, Yang Luhan's team at Harvard University successfully cloned the world's first endogenous retroviral active inactivated pigs. The birth of gene editing technology provides new ideas for scientists to promote allogeneic organ transplantation. If we can find genes in pig genes that cause rejection, blood clotting out of control, endogenous viral infections, etc., and knock them all out, it will effectively promote the development of organ transplantation.

"The organ transplantation technology is actually very mature, and the bottleneck is mainly due to the shortage of donors." Sun Hongtao said that the reason why scientists are so eager to continue to carry out research on xenotransplantation is because the gap in donors is too large, and patients die every day because they can't wait for donors. Although the number of organ donations and transplants in China has ranked first in Asia and second in the world, compared with the huge number of patients, it is still insufficient.

Sun Hongtao said that if the gene-edited allogeneic organ transplantation technology can really be realized, it will bring good news to the majority of patients who are waiting for organ transplantation. Usually, the rejection response of xenotransplantation will come quickly and violently, and at present, patients have not experienced serious rejection 72 hours after surgery, which has reflected technological progress. However, since the patient is still in the critical period after surgery, and he himself is also taking immunosuppressants to prevent rejection, the final efficacy still needs to be further observed.

(Pictured is the official website of the University of Maryland Medical Center)

(Original title: Why Choose Pig Heart? Experts interpret the world's first pig heart human transplant surgery)

Source: Beijing Daily Client | Reporter Liu Suya