Imma Perfetto
Cosmos science journalist
Researchers in China say they performed the first transplant of a genetically modified pig liver into a brain-dead human recipient, publishing their results in the peer-reviewed journal, Nature.
A liver transplant is the only cure for end-stage liver disease, which is responsible for an estimated 2 million deaths per year worldwide. But thousands of patients die awaiting an organ transplant each year.
Since the 1960s, clinicians and scientists have pursued experimental xenotransplantation – taking the organs, tissues, or cells from one species and transplanting them into another in experimental models – as a means to develop a solution to the unmet global demand for donor organs.
The recent transplant was carried out on 10 March 2024 at Xijing Hospital of Fourth Military Medical University in China.
The researchers say once in place, the organ secreted bile and produced porcine albumin, part of the process a normal functional liver performs.
“The graft function, [blood flow], immune and inflammatory responses of the brain-dead recipient were monitored over the subsequent 10 days,” they wrote in the paper.
During that time the xenograft maintained a stable blood flow and showed no signs of rejection, including hyperacute rejection most associated with xenotransplantation, the immune responses controlled by using a genetically engineered donor pig and using multiple immunosuppressive agents.
According to the paper, the study was terminated after 10 days at the request of the recipient’s family, which the researchers acknowledge “…made the follow-up period insufficient to analyse alterations in xenograft function over a long period.”
Dr Wayne Hawthorne, Immediate Past President of the International Xenotransplantation Association (IXA), and Professor of Transplantation at The University of Sydney, and Westmead Hospital in Australia, says that this is a “fantastic” step forward.
“Taking that translational step to go from the laboratory to large animals, to then clinical application, even in a brain-dead human setting where it is performed under a research protocol … it is still achieving another step towards ultimate clinical application.”
Why test brain-dead patients?
Hawthorne says that its safer, in some ways, to test xenotransplantation in a deceased patient before proceeding to a live recipient.
It gives surgeons the ability to take large biopsies and many samples from the organ and the recipient over a short period of time, which they cannot necessarily do in a live recipient who will recover.
“Within the first week, you generally come to major barriers in organ transplantation. You potentially can come up against severe rejection issues, or other issues such as primary non-function of a graft,” says Hawthorne.
“If you’re putting the organ into a live patient and you haven’t addressed all of these issues it may lead to serious complications and loss of the graft and or the patient… that’s the advantage of a brain-dead recipient.”
But only, Hawthorne stresses, provided it is done in an ethically approved, consented manner. The family of the brain-dead patient must fully consent to and register as undertaking the procedure under an approved research consented protocol and the regulations of that jurisdiction.
“The IXA is fully supportive of these sorts of studies prior to going to clinical trial, provided and underpinning this is the consent and the ethics,” says Hawthorne.
To ensure this happens, documents termed “The Changsha Communiqués” have been produced in partnership between IXA, The Transplantation Society, and the World Health Organization (WHO), to establish the Guidances and regulatory requirements internationally for xenotransplantation trials.
According to the Nature paper: “After receiving a detailed overview of the study procedures, the recipient’s 4 immediate family members signed an informed consent.”
“We’re hopeful that all these groups do provide the data for these studies to go on to the registry under the Human Xenotransplant Inventory,” says Hawthorne.
“We only ever want this to be done in an ethical and humane fashion.”
The inventory was established in 2006 with the main goal of making information “more accessible to the broader transplantation community, the public, and officials, fostering transparency, and thereby promoting best practices within the xenotransplantation field.”
This latest research was carried out to trial xenotransplantation as a bridge therapy for individuals with liver failure who are waiting for a human liver, with the aim of ultimately achieving a permanent transplant from a human donor.
