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Chinese scientists in Guangzhou have transplanted the first pig lung using genes edited with CRISPR technology. This key event could jumpstart transplantation research that has the potential to save thousands of lives.
Status Quo for Organ Transplants
Organ transplantation is the process of using another’s organs to replace a failing organ in the body. These organs can come from someone who has died and previously agreed to donate their organs or, in certain cases, from someone who is alive. Living people can only donate certain organs that are not essential to living, like one of the two kidneys in humans. Organ transplants are essential because they allow patients with poor prognoses, often facing death, to continue living a healthy life. Yet for 100,000 patients needing a transplant at any given time, there are only 40000 transplants a year. Adding on to the problem, a transplant organ needs to be a perfect match for the blood type, tissue type, and antigens of the recipient. Even a small chance of the body recognizing the transplanted organ as a foreign body could cause the immune system to attack, resulting in transplant rejection. Availability is low, and transplantations can cost hundreds of thousands or millions of dollars.
This is where xenotransplantation comes in. Xenotransplantation is defined as the interspecies organ transplantation (such as from pigs to humans) in contrast to allografting, which is conducted using human donors and recipients. Xenotransplantation can exponentially save more lives because it gives patients access to a larger pool of organs as potential matches. The technique is promising, and clinical results are starting to show great potential. The medical sector has been doing these transplants since the 17th century. In the 1960s, it wasn’t very common to be able to procure human organs, so many scientists and researchers looked into animal alternatives. A 1964 transplantation of a chimpanzee’s kidney to a human with end-stage renal disease ended up extending the patient’s life by nine months. The problem, however, was that these transplants were seen as foreign bodies by the recipient’s immune system, causing the patient to die within days. The discovery of cyclosporine, a strong immunosuppressant, in 1976 helped combat this problem, but there were still results of transplant rejection. The introduction of genetically engineered pigs was what started the trajectory towards a life-saving solution.
Pigs in Xenotransplanting
Pigs naturally have chromosomes and genomes that are similar to humans. With genetic modification, pigs are able to serve as organ donors with reduced rejection chances and infection transmission. This, combined with immunosuppressant medication, allows for longer living times for those with failing organs. This is why pigs were first used in xenotransplantation in 1968, with their organs being transplanted to baboons. After that, pig organs were tested in chimpanzees and rhesus monkeys, but the transplant failed. The introduction of genetic modification in 2003 made pigs better suited to xenotransplantation in humans. Currently, genetic modification in pigs is aimed at xenoantigens, complement pathways, and coagulation cascades to decrease the chances of rejection and increase survival for those who get the transplant.
The most promising development in recent times was the xenotransplantation of a pig lung in China. After battling with a brain hemorrhage, a 39-year-old man was declared brain dead, when scientists at Guangzhou Medical University transplanted a genetically altered pig lung into his body. CRISPR technology altered three pig genes in the lungs commonly targeted by the human immune system. The last-minute transplant kept the man alive for 9 days before it was removed due to graft dysfunction and eventual acute antibody-mediated rejection.
The Future of Xenotransplantation
Although the transplant in China didn’t last long, there were no signs of hyperacute rejection in the patient, which provides hope for future improvements to the xenotransplantation field through genetic modification. Of course, this transplant wasn’t perfect, and scientists in a publication of Nature Medicine argue that much more immunosuppression protocols, genetic modification, and preservation techniques will be needed; however, the importance of the China transplant lies in the organ used. There are already two patients currently living off of pig kidney transplants, but pig lungs are incredibly difficult to preserve because of increased air exposure and the amount of blood flow that goes through them. This ends up making it harder for patients who need the transplant to get a properly preserved organ. Today, there is a huge demand for lung transplants across the world. In the EU, 1705 patients were not able to get treated with a transplant, 216 of whom died before they could get one, whereas in the US alone, the waitlist for lung transplants increased to more than 3,200.
Reports of similar cases are rising, and the time for innovation is now. With more research into xenotransplantation from pig lungs to the human body, thousands of people on the waitlist could have another chance to live. The lung transplant by the scientists at Guangzhou proves that the future of xenotransplantation is in genetic modification.
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