Penn Medicine’s Porcine Liver Test Case Shows Promising Results for Transplant Patients

Penn Medicine’s Porcine Liver Test Case Shows Promising Results for Transplant Patients

University of Pennsylvania surgeons announced Thursday that they have successfully attached a functioning pig liver to the body of a recently deceased person, a pivotal test case for one day implementing the procedure to help living patients.

The surgeons used a pig liver that had been genetically modified using a precise gene editing technique called CRISPR, a key step that prevented the person’s immune system from rejecting the liver.

The recipient was declared “brain dead,” meaning he experienced permanent loss of brain function, said Abraham Shaked, the lead surgeon on the project at the Transplant Institute of Pennsylvania. But because the ventilator was still distributing oxygen throughout a person’s body, it was considered a valid testing ground for what it would be like to connect a pig’s liver to a live patient.

“It was amazing,” he said, describing the animal’s liver after it was delivered. “It was working.”

Elsewhere, other surgeons successfully transplanted pig hearts into two seriously ill human patients, extending their lives by a month or two. For now, Shaked and his colleagues have stopped doing this with pig livers, an organ much more complex than the heart. Instead, the initial proof-of-concept procedure, conducted in late December, involved attaching a pig’s liver to a person’s circulatory system through an external device.

Still, this was a major advance, others not involved in the project said. Even this intermediate step — connecting the pig’s liver to the patient through an external device — can serve as a “bridge” to recovery, said Jamie Locke, director of the Transplant Center at the University of Alabama at Birmingham.

She said exogenous pig livers could buy critically ill patients some time, keeping them alive until a donor human organ becomes available or until the patient’s liver has a chance to recover.

“This was the first step, and I think this was really valuable and important,” she said of the Penn study. “You can think of what they did as dialysis of the liver.”

The pig was raised in a secure facility by eGenesis, a biotechnology company based in Cambridge, Massachusetts, which funded the study. The company’s scientists edited the animal’s genome in 69 places so that the liver became compatible with the human body. Some modifications are designed to prevent rejection by the human immune system. Mike Curtis, the company’s CEO, said other modifications eliminated the risk of viral DNA inside the pig genome.

small pig

Furthermore, the animal was of a special breed, called the Yucatan piglet, which grows to just 150 pounds — large enough that its organs can be compared in size to their human counterparts.

Meanwhile, in Philadelphia, the nonprofit Gift of Life Program was on alert for any families of deceased patients who might agree to donate a body for this type of research.

Program coordinators identified such a family in December, and then a team from Pennsylvania headed to Massachusetts to retrieve pork livers from the eGenesis facility.

Liver function was preserved during the return trip by connecting it to a device made by OrganOx, a company based in Oxford, England.

After attaching the pig’s liver to the deceased person’s circulatory system, the Pennsylvania team monitored the organ for three days and did not detect any signs of inflammation or other problems.

Transplant surgeons hope that livers and other organs from genetically modified pigs will eventually provide at least a partial answer to the chronic shortage of donated human organs.

In 2023, even as the number of liver transplants exceeds 10,000 for the first time, many patients are still waiting. More than 900 people have died while waiting for a liver transplant, and nearly 1,000 patients have been removed from the waiting list because they became too sick to receive a liver transplant, according to the United Network for Organ Sharing (UNOS).

A gift for research

Shaked said Penn’s team now plans to repeat the pork liver procedure with additional donors, to measure how well pig livers filter toxins from the human bloodstream.

That will include obtaining consent from additional families who have lost loved ones, said Rick Haas, president and CEO of Gift of Life.

In such cases, surgeons must first determine whether the person’s organs can be used immediately for transplantation, he said.

But when that’s not the case, as happened in December in Pennsylvania, the deceased person can still play a broader role in the pursuit of science, Haas said.

“This is truly a unique opportunity to further advance the science of transplantation and have a significant impact on helping not just one, two, three or four patients, as most organ donors do,” he said. “It really could change the course of how end-stage liver failure is treated.”

(tags for translation) pig liver pennsylvania medicine genesis organox

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