Pig organs could provide temporary detox for people whose livers need time to recover or who are awaiting human donors.
By Smriti Mallapaty, March 20, 2024
In a milestone for the transplantation of animal organs into people, a 50-year-old clinically dead man in China has become the first person to receive a liver from a pig. With consent from the man’s family, researchers stitched the organ, from a genetically engineered miniature pig, to the man’s blood vessels, where it remained for ten days. It has been surgically removed today, says Dou Kefeng, one of the surgeons who led the transplant at Xijing Hospital of the Air Force Medical University in Xi’an. “Our study has just been terminated, and the colour and texture of the pig liver [transplant] are generally normal.”
The procedure was intended to test whether genetically modified pig organs could one day be used to supply hospitals for transplants. In China alone, hundreds of thousands of people experience liver failure every year, but only around 6,000 received a liver transplant in 2022. In the past few years, surgeons in the United States have transplanted pig hearts into two living people, and transplanted hearts and kidneys to several people declared dead because they lack brain function.
The Xijing surgeons say the pig liver secreted more than 30 millilitres of bile every day, a sign that it was functioning.
Researchers who specialize in transplanting animal organs into people, known as xenotransplantation, are eager to see more details about the procedure’s safety and functional benefits, and to learn from the work.
“This is a really exciting study,” says Ping Li, a transplant researcher at Indiana University School of Medicine in Indianapolis.
Important insights
The surgery marks the first time a pig liver has been transplanted into a human. However, in January, a team led by transplant surgeon Abraham Shaked at the University of Pennsylvania in Philadelphia connected a clinically dead person to a genetically modified pig’s liver located outside their body. The organ circulated the person’s blood for three days.
It is “heart-warming” to see researchers pursuing xenotransplantation all over the world, says Muhammad Mohiuddin, the surgeon and researcher who led the pig-heart transplants in living people. “It’s an expensive process, but it has a huge amount of potential,” says Mohiuddin, who is at the University of Maryland School of Medicine in Baltimore and is president of the International Xenotransplantation Association.
Luhan Yang, chief executive of Qihan Biotech in Hangzhou, China, which is developing gene-edited pigs as a source for organs, says she expects more xenotransplants in clinically dead people or — for compassionate reasons — in terminally ill people in the United States, China and Europe in the coming years.
The Chinese study will offer important insights into whether pig-liver transplants can keep people alive, even just for a few days, says David Cooper, a xenotransplant immunologist at Massachusetts General Hospital in Boston.
Ten days
On 10 March, the Xijing Hospital team, including Dou, Tao Kaishan and Wang Lin transplanted a pig liver weighing 700 grams into the donor, who lacked cognitive function. The surgery took roughly nine hours to perform. The donor received a daily regimen of immunosuppressive drugs, and his original liver was left in place.
The liver came from a Bama miniature pig (Sus scrofa domestica) bred by the company Clonorgan Biotechnology in Chengdu, China. It contained six genetic modifications, says Wang. These deactivated three genes for proteins found on the surface of pig cells and introduced three genes for human proteins, to prevent the donor from rejecting the pig organ.
Dou says the pig was bred in a specialized pathogen-free facility and tested negative for about a dozen pathogens, including Streptococcus suis, the type-2 strain of Mycoplasma pneumoniae and porcine cytomegalovirus. So far, he has not seen signs of an immediate form of organ rejection and the liver is producing bile. “This is encouraging,” says Cooper.
The researchers have also taken daily blood samples and liver biopsies and will assess immune response, infection risk and liver function in detail. “We’re having a pathologist evaluate if there’s acute rejection,” says Dou.
The surgery was approved by the recipient’s family and several university committees, says Wang. “It has been strictly carried out according to relevant national and international regulations.”
Temporary fix?
The researchers plan to repeat the procedure in another clinically dead person later this year — and next time they will remove the person’s existing liver.
Mohiuddin points out that although clinically dead people are a useful model for assessing the viability of xenotransplantation in living people, that usefulness is limited, because once a person’s brain ceases activity, they undergo hormonal changes. And it isn’t yet clear how long someone with no cognitive function can be maintained on a ventilator and with a donated pig organ, he says. The longest documented case was two months, which involved a pig-kidney transplant.
Shaked also questions whether surgery is necessary for pig livers to be useful to humans. Unlike the heart, which essentially functions as a pump, the liver performs many complex tasks, which makes it particularly difficult to transplant. A pig liver can carry out the liver’s detoxifying and waste-disposal role, but Shaked does not anticipate that it will be able to produce the broad array of proteins required for the human liver’s other functions.
This means that whereas heart and kidney xenotransplants have been touted as possible long-term organ replacements, liver xenotransplants are seen mainly as a short-term fix for people with liver failure. They could enable a person’s existing liver to regenerate, for example after damage caused by alcohol or drug consumption, or could buy time while waiting for a human liver donor.
As a result, Shaked and his team chose to avoid operating: they hooked up an external pig liver to the recipient using blood-carrying tubes. But Dou says his team’s goal is organ replacement. He adds that working in a person allows the researchers to collect a lot more data, including information on immunology and physiological changes.
Yang says she hopes the team will publish detailed insights about the transplantation in peer-reviewed publications, to help determine which approach is more feasible.
In the meantime, Shaked hopes to exchange notes with the Chinese team. “I’d love to hear more about what they did. It’s fantastic.”
(Sources: Nature)
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