Credit：Medicine.net
Organs are an integral part of the body for all people. For those who have health problems with their own organs and are in need of an organ replacement, it is especially important to find a replacement for an organ that is no longer functioning properly. Today's sophisticated organ transplants are based on human-to-human organ replacement, but for this reason, matching organs are rare and many patients are in danger of being left without a replacement. For this reason, many researchers have conducted extensive studies on the use of organs from other species to replace specific organs in humans.
Which species did humans choose?
In 1984 and 1992, humans attempted to use the organs of baboons, an animal relatively similar to humans, for human transplants, but unfortunately, the patients died shortly after the transplants were performed due to rejection of the organs. In addition, in foreign research on infectious diseases, it was found that animals similar to humans, such as orangutans and baboons, could easily transfer the viruses they carry to humans through organ transplants, which has led to a search for new other species to replace them.
Researchers have found that pigs and humans have similar food habits, metabolic levels, body temperatures, heart rates, and so on, which gives humans a whole new choice of species for xenotransplantation. Additionally, the viruses in pigs, because of their relatively large species span, are not easily transmitted to humans. In 2003, the Revivicor company creatively genetically modified a cloned pig to breed the first generation of genetically modified pigs in an attempt to overcome the ‘biological barrier’ between pig organs and humans in transplantation, which has now become the globally recognized basis for organ donation. Of course, in order to better eliminate the risk of infection in pig transplants, in 2015 the Harvard team knocked out the PERV gene by means of gene editing. With this kind of problem solved, pig organ transplants became more feasible.
Humans receive pig organ transplants
In January 2022, 57-year-old David Bennett received a porcine heart transplant, the first time a living human had received such a transplant. The patient achieved freedom from ECMO on the fifth day after the transplantation, which inspired researchers studying cross-species organ transplants, as well as patients waiting for organ transplants. However, two months later, the University of Maryland Medical Center (UMMC) in the United States announced the patient's death. According to the autopsy report provided, the patient's death did not correspond to previous cases of xenotransplant rejection. After more than a year of investigation, the UMMC team released a detailed report in The Lancet, stating that the patient died of heart failure caused by poor health and a severely compromised immune system prior to transplantation, two injections of immunoglobulin (IVIG), which may have damaged the cardiomyocytes, and the detection of porcine cytomegalovirus. The report suggested that the patient's death was not due to organ rejection, which gives hope for future xenotransplantations.
In September 2023, UMMC again announced the successful completion of a pig heart transplant. However, the patient, like the first living human pig heart transplant recipient, eventually passed away. In March 2024, Massachusetts General Hospital announced the completion of the world's first living human porcine kidney transplant, which was very successful. The patient recovered well post-transplant, but on May 7, 2024, the patient died. The surgeon who performed the transplant, Tatsuo Kawai, revealed that the patient's kidneys had still been functioning well the day before his death, and that his death was unrelated to the transplant.
In April 2024, NYU Langone Health announced that a combined mechanical heart pump (LVAD) and gene-edited porcine kidney and porcine thymus transplant was performed from April 4 to April 12, 2024. Learning from the experience of previous deaths from porcine heart surgeries, the team transplanted the porcine thymus at the same time as the porcine kidney to help fight rejection. The patient is now recovering well, and the team continues to follow up on the patient's health.
In May 2024, the First Affiliated Hospital of Anhui Medical University announced that it had completed the first porcine liver transplant in a living human on May 17, 2024. The patient recovered well and was able to get out of bed and move freely on the seventh day after the operation. No hyperacute or acute rejection has been detected, and the team is continuing to track the patient's physical condition.
How long will it take to organ transplants across species?
In fact, an article published in 2023 suggests that non-human primates that received pig kidney transplants survived for more than a year. Robert Montgomery, a transplantation surgeon at New York University, says "cross-species transplantation in humans has not been as great a success as predicted for other primates." But he also said "it's not an insurmountable problem" and "I'm encouraged that we've come so far."
Humanity around the globe is looking forward to the success of interspecies transplants to prolong and improve the lives of patients in need of treatment. With a total of five porcine organ transplants in living humans from the first porcine heart transplant in 2022 to the completion of porcine liver transplants in 2024, and more porcine organ transplants in brain-dead patients, we need to be grateful to this group of people for their contributions to medicine. Because of their contributions, there was only one living human pig transplant in 2022, while three living human pig transplants have now been completed in 2024. The medical community is generally optimistic about pig organ transplants, and many medical experts believe that pig organ transplants may greatly extend the lifespan of patients in the near future. Perhaps, in the near future, humans will no longer have to worry about the shortage of organs.
Reference：
1.https://www.nature.com/articles/d41586-024-01453-2
3.https://www.massgeneral.org/news/rick-slayman-family-and-mgh-statements
5.Mohiuddin, Muhammad M et al. “Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report.” Lancet (London, England) vol. 402,10399 (2023): 397-410. doi:10.1016/S0140-6736(23)00775-4
6.https://www.nature.com/articles/s41591-024-02972-1
7.https://mp.weixin.qq.com/s/z_g675KR-E58vBQWubNd9Q
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