Science

Xenotransplants: Modified pig hearts transplanted into dead

Researchers at NYU have successfully transplanted two genetically modified pig hearts into recently deceased humans who were kept on ventilators.

Health



12 July 2022

Nader Moazami, MD, (right) surgical director of heart transplantation at the NYU Langone Transplant Institute, and cardiothoracic physician assistant Amanda Merrifield prepare to remove the heart from a recently deceased donor on Wednesday, July 6, 2022, in New York, NY.

Surgeons at NYU Langone prepare to remove the heart from a recently deceased donor ahead of a modified pig heart transplant

JOE CARROTTA/NYU LANGONE HEALTH

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

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 of 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’s Tisch Hospital in New York City. The first recipient was a 73-year-old man, Larry Kelly, who had previously undergone two open heart surgeries. Information on the second recipient has not 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; 17 of them die each day. The main concern with using animal organs, however, is transplant rejection – when the immune system attacks the organ, eventually causing organ failure.

Caption: A genetically modified pig heart suspended in solution ahead of xenotransplantation at NYU Langone Health on Wednesday, July 6, 2022, in New York, NY. Credit: Joe Carrotta for NYU Langone Health

A genetically modified pig heart suspended in solution ahead of xenotransplantation on 6 July in New York, NY

JOE CARROTTA/NYU LANGONE HEALTH

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 patients 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 to ensure 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 says 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 phase I clinical trials of heart xenotransplantation will occur within the next few years. In the meantime, he says 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.”

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