In the past year, doctors have performed history-making transplants, placing genetically modified pig kidneys and pig hearts into patients. Now, a group of doctors and scientists in China report they have done the same with a pig liver.
In a study published in Nature, the group describes transplanting a gene-edited pig liver into a brain-dead patient. At the request of the patient’s family, the study was terminated after 10 days and the pig liver was removed. The patient’s original liver was not removed, so the experiment served as a way to test whether a pig liver could supplement the function of failing livers for patients waiting for a transplant.
“The transplanted pig liver successfully secreted bile and produced liver-derived albumin, and we think that is a great achievement,” said Dr. Lin Wang, a surgeon at Xijing Hospital, Fourth Military Medical University and one of the senior authors of the paper, during a briefing. “It means the pig liver could survive together with the original liver in a human being—and would give additional support to an injured liver, maybe, in the future.”
Pigs are promising sources of organs, but the human immune system rejects transplanted pig tissue. Scientists have been getting around this by genetically modifying the pigs that provide the organs. The donor liver in this case came from a pig that had received six modifications to certain genes in order to remove major pig proteins that would have led to rejection; the editing technique also added genes that made the liver appear more human to immune cells.
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Earlier this year, a surgical team at the University of Pennsylvania reported connecting a brain-dead patient to a gene-edited pig liver that remained outside of the patient’s body, but the results were not published in a peer-reviewed journal. In the Chinese case, Wang and his team transplanted the liver into the patient, connecting major blood vessels to monitor how well it could produce key compounds like bile and albumin.
Wang said the blood flow to and from the liver, as well as measures of things like bile and albumin production, were encouraging, even if not all functions were sufficient enough to completely mimic a human liver. There were changes in platelets and clotting functions soon after the transplant, but those seemed to resolve after a few days. The pig liver began producing bile two hours after the transplant, and levels of albumin began increasing as well following the operation. When the team analyzed the liver after removing it 10 days later, there were “no signs of immune rejection,” they wrote in the paper.
The transplant came after about a decade of earlier studies and transplants by Wang and his team of gene-edited organs from pigs into monkeys, including a pig heart, kidney, cornea, and bone. The group also performed a skin transplant using gene-edit pig skin into a person with severe burns.
The liver has remained a challenge to transplant with anything other than another human liver, since the organ performs so many complex functions, Wang said in the briefing. “The heart functions as a pump to pump blood to the whole human body, and the major function of the kidney is to produce urine,” he said. “However, the liver has so many functions. It has functions in digestion, to make cytokines [that regulate the immune system], and produce albumin. This is a great achievement because it is the first time we can unravel whether a pig-derived liver could function well in the human body or could successfully replace a human liver in the future.”
Wang said the team has also transplanted a pig-edited liver into a brain-dead patient after taking out the patient’s liver, and is currently monitoring how well the organ can function on its own. He is hoping to conduct additional transplants, both mimicking the current study in which the pig liver functions along with the patient’s liver, as well as replacing patients’ liver entirely, in the coming year.
