Experimental transplant of gene-edited pig liver into human offers hope for new frontier of research

Doctors in China have become the first to report details about a transplant of a genetically modified pig liver into a human.

The liver was transplanted last year into a person who was brain-dead, and it “functioned very well in the human body” for 10 days, the researchers said. The blood flow to the organ was good, and there were no signs of immune rejection or accumulation of inflammation.

“It’s a great achievement,” said Dr. Lin Wang, a co-author of the study published Wednesday in the journal Nature.

With more than 100,000 people on organ transplant waiting lists in the US alone, the demand for human organs far outpaces the supply. Scientists have been exploring alternatives for decades, including using pig organs because of their similarity to human organs.

Last year, Penn Medicine did the first successful external liver perfusion using a gene-edited pig liver. Blood in a brain-dead patient circulated through a pig’s liver that was outside the person’s body. In that case, the pig’s liver showed no signs of inflammation in the 72 hours it was tested and the patient’s body remained stable.

Researchers have had some successes transplanting gene-edited pig kidneys and hearts into people, but liver transplants have proven to be more complicated.

“The heart just functions as a heart to pump the blood. The major function of the kidney is to produce the urine. The liver has so many functions,” Wang, a surgeon in the Department of Hepatobiliary Surgery at Xijing Hospital in Xi’an, China, said Tuesday.

The liver filters the blood, removing toxins and waste; processes nutrients; detoxifies harmful substances like alcohol and drugs; produces bile to help with digestion; produces proteins that help the blood clot; and plays an important role in regulating blood sugar.

Working with the liver “is so difficult,” Wang said. “We all know the function of the liver is so complicated.”

Replacing a human organ with a pig’s is complicated, said Dr. Shimul Shah, an expert in xenotransplantation — the transplant of animal organs into humans — and division chief of abdominal transplantation in the Integrated Department of Surgery at Mass General Brigham.

The liver is a larger organ with a dual blood supply, meaning it gets blood from two sources: the hepatic artery bringing oxygenated blood and the portal vein that brings nutrient-rich partially deoxygenated blood from the digestive organs.

“We’ve done a much better job in kidney and heart and, even in the near future, in lung,” said Shah, who was not involved with the new report. “Liver is going to take a little bit more time.”

As of September, more than 9,000 people in the US were waiting for a liver transplant. It is the second biggest need on the transplant list, following only kidneys. according to the Health Resources & Services Administration.

A successful pig liver transplant would be a major advance for people with acute liver failure, even as a temporary bridge while awaiting a human donor organ. By the time most of these patients make it to the hospital, Shah said, their livers are so damaged that a transplant is the only option.

“You can’t take out someone’s liver and not give them something that is going to function in the meantime,” Shah said. A pig organ may be a good fit in this situation.

The newly documented transplant was conducted in March 2024 in China.

To make the organ more compatible with the human body, scientists made six gene edits to a liver from a Bama miniature pig.

When the surgeons placed the pig organ in the patient, they still kept the human liver in place. Wang said he wasn’t sure whether a pig liver could ever fully replace a human’s, since the volume of material that the pig liver produces may not fulfill what a human body requires.

Separate from Wednesday’s study, the team in China said it has also conducted a pig-to-human liver transplant that involved removal of the human organ, but details about that procedure have not been released.

In the newly published case, the researchers terminated the experiment after 10 days at the request of the family.

Wang said the new work builds on what the researchers have learned about xenotransplantation from surgeons in the US who have had some success with transplanting kidneys and hearts. It also builds on their own work with animals.

In 2013, Wang and his colleagues were the first in China to successfully transplant a pig liver into a monkey, which survived 14 days. The team said it has also done pig-to-monkey heart, kidney, cornea, skin and bone transplants.

Wang says the team also recently transplanted a pig kidney into a human, and that patient should be well enough to go home soon. Details of the case have not yet been published.

Shah has been a part of the team at Mass General Brigham that successfully transplanted a pig kidney into a human who is currently doing well enough to live at home. He believes that the science is not quite there yet for the liver.

“I think this will help us understand, how do we advance liver xenotransplantation? Because we need more work like this,” Shah said of the new research.

Incremental steps help doctors get a step closer to fulfilling the ultimate goal of being able to offer a transplant to everyone who needs one, said Dr. Parsia Vagefi, chief of surgical transplantation at UT Southwestern Medical Center.

Doctors have experimented with liver dialysis and medicines to treat people with acute liver failure, said Vagefi, who wasn’t involved with the new research, but “nothing’s really moved the needle yet, aside from transplantation, to really help that population.”

“This shows it really may help bridge someone,” she said of the new study.