Recently, the "world's first pig heart transplant" has attracted many people's attention. According to Xinhua News Agency, medical experts from the University of Maryland School of Medicine and the University of Maryland Medical Center have successfully performed a special transplant for an American male heart patient, transplanting the heart of a genetically modified pig into his body, which is the first case in the world. The man was in good condition 3 days after surgery.
Doctors will assess the success of this transplant in a few weeks' time, "and over the next few to several weeks, patients will be closely monitored to determine if the transplant is life-saving." "In the view of the surgical medical team, if this operation is finally considered successful, it will bring hope to many patients around the world who are waiting for organ transplants."
As soon as the news came out, it aroused everyone's curiosity and concern: "Why do scientists and doctors choose pig hearts as donors?" "Does that mean a successful xenograft?"
Xinhua Photo
Status: There is a serious shortage of transplanted organs worldwide
According to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, at present, there is a serious shortage of transplanted organs around the world, and people are dying every day while waiting. In China, there are as many as 1.5 million patients with advanced heart failure every year, but about 500 to 600 patients can really receive transplants.
Heart transplantation is basically not difficult in terms of surgical techniques, the success rate of surgery is more than 95%, and the survival rate of one year after surgery is 94 to 95%. The first heart transplant in China, and the first in Asia, was completed in 1978. Since then, heart transplants have been carried out continuously in China, and there have been reports of patients surviving for more than 20 years after transplantation. Therefore, the difficulty of heart transplantation is still a big contradiction between the shortage of heart transplant donors and the large number of patients with advanced heart failure who need to receive heart transplantation.
According to Professor Zhao Qiang, vice president of Ruijin Hospital and expert in cardiac surgery, in order to solve the dilemma of the shortage of transplanted organs, scientists have turned their attention to animal organs. However, the rejection response of xenotransplantation between different species is stronger than that of all-species transplantation, so scientists have adopted the method of genetic modification.
Why choose a pig heart?
Xenotransplantation research provides more options for solving the "transplant organ shortage", but at the same time faces technical difficulties such as xenovirus transmission and immune compatibility. According to Xinhua News Agency, there are two major medical risks in transplanting pig organs into humans: pigs' genomes carry endogenous retroviruses, which may be "toxic" after transplantation into humans; pig organs may trigger immune rejection in patients.
According to Agence France-Presse, the pigs who received the hearts of the above-mentioned pig heart transplant patients were genetically modified and involved a total of 10 specific gene edits. The researchers knocked out three genes on the pig chromosome that may cause the body to reject the pig heart, knocked out one gene that may cause the pig heart tissue to overproliferate, and implanted six human genes into the pig chromosome that help the body accept the xeno organ to enhance the pig organ's tolerance to the human immune system.
According to Professor Zhao Qiang, the size of the pig's heart and the human heart are close. From the perspective of the origin of species, it is far from humans, so there are fewer zoonotic diseases, with the development of gene editing technology, scientists can cut off the gene expression of pigs, transfer human genes to the heart of pigs, so that after the heart of the pig is transplanted into the human body, the rejection response will be reduced. And pigs can reproduce quickly, so it is more appropriate for doctors to choose pigs as a source of xenosis for donors.
Many countries have tried to carry out xenotransplantation studies with pigs
In order to solve the shortage of transplant organs, many countries are trying to carry out xenotransplantation research with pigs, and some breakthroughs have been made in recent years. According to Xinhua News Agency, researchers in China and the United States and other countries reported in 2017 that they used gene editing technology to "knock out" all endogenous retroviruses in the pig genome, and the organs of these pigs would not be at risk of related viral infection if transplanted to humans.
Research on immune compatibility is also making progress. Mayana Zatz, a professor at the Institute of Biological Sciences at the University of São Paulo in Brazil, reported in 2019 that scientists have identified three genes in pigs that can cause the human rejection response, and turning off these genes with gene editing techniques such as CRISPER/Cas9 has the potential to eliminate rejection of pig organs by the human immune system.
With these scientific research advances, the transplant surgery carried out in the United States has made a new breakthrough. According to reports, in order to improve the success rate of surgery, the scientific team has previously tried to transplant the heart of pigs into 50 baboons for experiments to study the response to postoperative reactions such as immunosuppression, hypotension, and obstruction of blood clotting. Before the pig heart transplant, in October last year, American researchers successfully transplanted the genetically modified pig kidney to the thigh of a brain-dead patient with renal insufficiency, although the in vitro observation experiment lasted only three days, but there was no rejection reaction.
Does this mean that the xenograft was successful?
Professor Zhao Qiang said that once this technology is successful, it will bring new dawn to heart transplantation, kidney transplantation and liver transplantation and solve the problem of donor shortage. However, xenotransplantation still has multiple ethical and technical problems, which need to be further studied and discussed. For example: Is there more rejection than all-in-one transplantation? After the pig's tissue is transplanted into the human body, will it form a chimera with the human immune system, will it be passed on to the offspring, or will it have a negative impact on human evolution? Ethically, how does the recipient of a pig's heart identify with himself? What does society think of him? These issues require our attention.
According to reports, the peak of the development of transplant technology, taking heart transplantation as an example, is to use the patient's own cells to create an artificial, flesh-and-blood heart through laboratory culture, such a heart is theoretically a perfect donor. In terms of genomics and immunotechnology, China is closely following the international frontier, but we have not made progress in tissue cultivation.
Whether genetically modified organ transplantation is for the benefit of mankind or opens a Pandora's box, this needs to be constantly discussed and improved in terms of ethics, laws and regulations.
Synthesized from Xinhua News Agency, WeChat public account of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
Finishing: Nandu reporter Li Zhiqi