来源: Nature    时间:2024年06月08日    浏览量:

By Smriti Mallapaty

A 71-year-old man in China has become the first living person to receive a liver transplant from a genetically modified pig — and the fifth person reported to have received a pig organ. More than two weeks after the surgery, the man is “doing very well”, says Sun Beicheng, a surgeon at the First Affiliated Hospital of Anhui Medical University in China, who led the transplantation.

The surgeons have not released many details about the procedure, but researchers are encouraged by the apparent success. “It is very exciting news,” says Burcin Ekser, a transplant surgeon at Indiana University School of Medicine in Indianapolis.

The liver is the latest in a series of pig organs introduced to people. Since early 2022, surgeons have transplanted pig hearts, kidneys and a thymus into four people. Three of them died in the months after receiving their transplants, although researchers say that their pre-existing poor health, which contributed to their selection as transplant candidates, makes it difficult to determine whether the transplants were a factor. One person who was operated on in mid-April is still alive today.

The transplants have allowed researchers to gain valuable insights into the feasibility of xenotransplantation — the transfer of organs from one species to another. Clinicians hope the procedure might one day supply organs to the thousands of people who die each year while waiting for a donor organ.

Xenotransplantation of livers has surged this year. In January, a US team connected a genetically modified pig liver outside the body of a clinically dead person. In March, Kefeng Dou, a transplant surgeon at Xijing Hospital at the Air Force Medical University in Xi’an, China, and his colleagues transplanted a genome-edited pig liver into a clinically dead individual. The liver remained in the body for ten days and saw no signs of rejection. And in May, another team in China transplanted a pig kidney and liver into a clinically dead person. 

In the most recent pig-organ transplant, the recipient had a large tumour on the right lobe of his liver, which had not yet spread to other parts of the body. The individual was not eligible to receive a human-liver transplant because tests indicated that his liver was functioning too poorly to ensure a good outcome — his liver’s left lobe alone would not be able to keep him alive, says Sun. The physicians didn’t know “when the tumour would rupture”. With few other options, Sun says that the individual and his family expressed interest in the xenotransplant. The surgery team obtained approval from their hospital’s ethics and transplantation committees on compassionate grounds. 

On 17 May, in an operation that lasted eight hours, surgeons removed the individual’s right lobe. They replaced it with a 514-gram liver from an 11-month-old miniature pig that weighed 32 kilograms.

The pig had ten genetic modifications to prevent its organs from being rejected by the recipient’s body, says Hong-Jiang Wei, a geneticist at Yunnan Agricultural University in Kunming, China, whose team developed the pig. The team deactivated three genes that contribute to the production of sugars on the surface of pig cells, which the human immune system attacks, and introduced seven genes that express human proteins.

Sun says that the team did not detect the presence of porcine cytomegalovirus in the liver, which could have contributed to complications in a recipient of a pig heart, who died two months after the procedure.

Save or support

Once the surgeons had re-established blood flow to the transplanted pig liver, it instantly began to secrete bile. Bile production gradually increased to between 200–300 millilitres on day 13 (a healthy person secretes at least 400 mL of bile a day).Sun says that he has not seen signs of the organ being rejected, including from a biopsy conducted on day 12. “He has normal liver function,” says Sun. 

“That is a very positive result,” says Jay Fishman, a specialist in transplant infectious diseases at Massachusetts General Hospital in Boston. “You don’t see those kinds of good signs if the organ is suffering rejection.” However, he cautions that signs of chronic rejection could appear later.

As well as bile, Sun says that the pig liver is producing pig versions of albumin and coagulation factors. From the way that these essential proteins function, “we may learn a great deal”, says David Cooper, a xenotransplant immunologist at Massachusetts General Hospital. Researchers might learn whether future transplants will need to genetically manipulate the pigs to produce the human versions of those proteins. 

Sun hopes that ultimately the person’s left liver lobe will grow large enough to provide full liver function and that the pig liver will serve as a bridge to get to that point.