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Penn Medicine surgeons successfully attached a pig liver to a brain-dead human body. Credit: Anna Vazhaeparambil

Penn Medicine surgeons successfully connected a genetically modified pig liver to a recently deceased person’s body — bringing doctors one step closer to performing the procedure in live patients with liver failure.

In December 2023, the research team successfully circulated the blood of a recently deceased human donor with a pig liver outside of the body, an approach called extracorporeal perfusion. The novel experiment offers a new method for addressing the chronic shortage of human organs for transplantation, as more than 10,000 patients nationwide are waiting to receive a liver transplant.

Prior to the transplant, the recipient of the pig liver was declared brain-dead and kept alive by a ventilator that circulated oxygen throughout the person’s body. The liver used in the procedure came from a pig genetically edited using CRISPR gene editing technology to be compatible with the human immune system.

This modification was needed in order to prevent the organ from being rejected by the human body, a common hurdle faced in previous attempts of xenotransplantation — transplantations into a human from a nonhuman source.

Rather than implanting the pig liver inside the body, the surgeons connected the liver externally through a machine while the donor’s liver was kept in place inside the body. This technique could potentially serve as a “bridge” to transplant for critically ill patients until a human liver becomes available. This approach could provide an alternative option for cases of liver failure, in which options were previously limited.

During the 72-hour study period, the pig liver showed no signs of inflammation and the donor’s body remained physiologically stable. 

According to a Penn Medicine news release, the research team will refine the procedure for experiments with three additional deceased donors and study the approach in deceased donors whose livers have been removed.

“Any time a patient dies while waiting for a transplant, it is a tragedy, and we are always working to develop new ways to extend their lives,” lead surgeon and director of the Penn Transplant Institute Abraham Shaked said in the news release.

This experiment took place through collaboration with eGenesis, a biotech firm specializing in genetic modifications, which produced the organ from a Yucatan mini pig — a breed small enough for its organs to be comparable to human ones. The pig’s genome was edited in 69 places to ensure compatibility and safety for human use, eliminating risks such as immune rejection and viral transmission from the pig to the human body.

Continued success in experiments such as these has the potential to alleviate demand for liver transplants. Transplantation is the only definitive cure for liver failure, and the wait time for a transplant can take up to five years, according to Penn Medicine. In 2023, over 900 patients died waiting for a liver transplant, according to the United Network for Organ Sharing.