Surgeons have transplanted a lung from a genetically modified pig into a brain dead human recipient for the first time and found it functioned for nine days, researchers have revealed.
The work is the latest development in a technique called xenotransplantation that is aimed at solving the organ shortage crisis: according to the World Health Organization, only up to 10% of the global need for such transplants is being met.
However, experts have stressed there is a long way to go before pig lungs can be used in patients.
Dr Justin Chan, a lung transplant surgeon for the NYU Langone Transplant Institute who was not involved in the work, described the study as “exciting and promising work”, but said the report concerned only one patient and was a “qualified success”.
“These lungs are not able to independently sustain a patient,” he added.
Andrew Fisher, a professor of respiratory transplant medicine at Newcastle University, agreed. “This work is very welcome in furthering our understanding, but it marks an incremental step forward. There is much more work required and we are not on the dawn of an era of lung xenotransplantation using pig lungs,” he said.
Xenotransplantation has become a hot area of research in recent years, with the heart, kidneys and liver among the organs that have been transplanted into humans from pigs. The latter are typically genetically modified by removing certain pig genes and inserting specific human genes, to reduce rejection of the organs by the recipient’s body.
Studies are often initially carried out on brain dead human recipients before, in some cases, being used in living patients. While there have been only a handful of living recipients, many have died within weeks or months of such surgery, albeit not necessarily from complications relating to the transplant. However, some with transplanted pig kidneys have survived with the organs still functioning several months after the procedure.
But experts say xenotransplantation using lungs is particularly tricky.
“Every breath you breathe in is bringing the external environment into the body,” said Fisher. This means the lungs need to be very capable of responding to attacks from pollution, infection and other sources. “So the immune system in the lung is very sensitive and very active, which means when you’re dealing with organ transplantation, where you know you don’t want the immune system to be very active, it poses extra challenges.”
Writing in the journal Nature Medicine, researchers in China reported how they transplanted the left lung from a Chinese Bama Xiang donor pig with six genetic modifications into a 39-year-old brain dead male recipient.
The team found the lung remained viable and functional over a 216-hour period and did not trigger hyperacute rejection – a rapid, violent immune response by the recipient’s body. There were also no signs of infection.
However, 24 hours after transplantation the lung showed signs of fluid accumulation and damage, possibly initially due to transplant-related inflammation. And despite the recipient being given powerful immunosuppressive medication, the transplanted organ was progressively attacked by antibodies, resulting in significant damage over time.
“The impact of the damage was likely underestimated [because] the human recipient still had one of their own lungs present and this would have compensated for the damaged porcine lung,” said Fisher.
Prof Peter Friend, from the University of Oxford, said the results were complicated by the fact brain death itself causes an acute inflammatory state. “So some of what they are seeing may be a function of the brain dead status of the recipient,” he said.
The researchers behind the work said the approach needed to be refined.
“Continued efforts are needed to optimise immunosuppressive regimens, refine genetic modifications, enhance lung preservation strategies and assess long-term graft function beyond the acute phase,” they wrote.
Friend said other approaches to increasing the availability of organs were being investigated, including remodelling donor organs using stem cells.
Some research groups are also exploring the possibility of growing humanised organs inside pigs or sheep.
Fisher added that while xenotransplantation for lungs held promise, another promising avenue was to treat human donor lungs deemed to be unsuitable for transplantation so they could be used.
“If we get that right, that’s something can be implemented within months, and certainly in years could be making very big differences,” he said.
