Modified pig hearts transplanted into dead people kept on life support

For the first time, researchers have successfully transplanted genetically modified pig hearts into two recently deceased humans who were on life support. The recipients, who had been declared brain-dead prior to the transplants, were kept on ventilators and dialysis both before, during and after the procedures.

Until last year, xenotransplants — or the transfer of animal organs to humans — had only been tested in non-human primates. The first xenotransplant in a deceased human on life support took place in September 2021 using a pig kidney.

Then, in January this year, the first living human, David Bennett, received a pig heart transplant, but died two months later for unknown reasons.

“It was a tremendous feat to keep [Bennett] alive for two months, but, in the end, we don’t really know why the heart failed and why he died, and that is the limitation of doing a one-off transplant in a living human,” said Robert Montgomery at New York University Langone Health at a press conference today. “That is the benefit of doing transplants in deceased humans. We are able to look at tissues and blood samples and get a much deeper analysis of what’s going on.”

The two surgeries took place on 16 June and 6 July at NYU Langone Health’s Tisch Hospital in New York City. The first recipient was Larry Kelly, a 73-year-old man who had previously undergone two open-heart surgeries. Information on the second recipient hasn’t yet been shared. The families of both people donated their bodies to science.

The transplants followed standard clinical procedures, said Nader Moazami at NYU Langone Health during the press conference. The two recipients were observed for 72 hours afterwards, and biopsies were taken daily. There were no signs of rejection and the hearts functioned normally, contracting and maintaining blood flow throughout the body.

Xenotransplantation offers a promising solution to the shortage of donor organs. In the US alone, more than 105,000 people are waiting for an organ transplant. Every day, 17 of them die. The main concern with using an animal organ is transplant rejection – when the immune system attacks the organ, eventually causing organ failure.

To avoid this, Moazami and his colleagues used hearts from pigs with 10 genetic modifications. Four turned off genes known to increase the risk of transplant rejection and abnormal organ growth. The other six inserted human genes that reduce incompatibilities between biological pathways in pigs and humans. Researchers also gave the recipients standard post-transplant medications to suppress immune response.

Infection with animal viruses is another possible risk of xenotransplants. For that reason, pigs bred for organ transplant live in special facilities with the aim of ensuring they are disease-free. Despite this, the pig virus porcine cytomegalovirus was detected in Bennett’s blood after transplantation. While the virus cannot infect human cells, it did infect the transplanted organ, potentially contributing to his death.

For the two recent xenotransplants, Montgomery said they used a more sensitive screening procedure that can detect low levels of this virus. They also developed specialised screening methods to monitor for the transmission of other pig diseases. No viruses were detected in either of the two pig hearts.

Montgomery hopes early-stage clinical trials of heart xenotransplantation will occur within the next few years. In the meantime, he said his team will focus on collecting as much data as possible from performing the operation in deceased humans and lengthening the observation period.

“It was one of the most incredible things to see a pig heart pounding away and beating inside the chest of a human being. It is a great privilege to witness that in my lifetime,” said Montgomery. “This is a completely new frontier.”