A monkey has survived for more than two years after receiving a pig kidney transplant in an “unprecedented” study, scientists have said.
Researchers said the finding offers hope for the potential of long-term use of pig organs in humans.
Scientists, led by experts from biotechnology company eGenesis and Harvard Medical School in the US, transplanted kidneys from genetically modified Yucatan miniature pigs into macaque monkeys.
The scientists made 69 genetic modifications to help prevent rejection of the transplanted organ and to help prolong survival.
The results are unprecedented and signify a monumental step forward for achieving human compatibility— Dr Mike Curtis, eGenesis
These edits included adding human genes, eliminating pig viruses and removing three antigen coding genes which play a role in “hyperacute rejection”.
Previous work identified that the three “glycan antigen genes” found in pigs are recognised by the human immune system and attacked, leading to rejection of the organ.
Scientists theorised that removing these genes would help prevent the monkeys’ bodies from rejecting the transplanted kidney.
Meanwhile, a significant proportion of the modifications were dedicated to removing the porcine endogenous retrovirus (PERV) gene.
While this gene does not cause disease in pigs, there is limited laboratory evidence that it can infect human cells.
And adding human genes to the pigs helps prolong survival of the transplanted organs, the scientists found.
Some 21 monkeys were given pig kidney transplants.
Among these, six were given kidneys which had been modified to remove the antigen genes and the PERV gene; eight received transplants which had removed the antigen genes and added the human genes; and seven of the donor kidneys had all three types of genetic modification.
Overall, the team found that the addition of human genes appeared to significantly improve survival rates.
Kidneys which were only edited to remove the antigen genes “exhibited poor graft survival”, experts said.
But those which were modified to carry seven human genes and “knock out” the antigen genes saw survival rates increase seven-fold and had an average survival of 176 days, according to the study.
One monkey survived for 758 days, according to the new study, which has been published in the journal Nature.
The researchers said their work brings clinical testing of genetically modified pig kidneys for human transplantation a step closer.
Dr Michael Curtis, chief executive of eGenesis, said the study marks a “significant step forward in transplantation and medicine more broadly”.
“Our most recent publication outlines the achievement of an extraordinary milestone that provides hope and paves the way to better outcomes for countless individuals in need of life-saving organ transplants,” he said.
“The global burden of kidney disease is staggering.
“Cross-pieces transplantation offers the most sustainable, scalable and feasible approach for delivering new sources of organs to patients.
“Our proof of concept study published this week shows for the first time durable long-term survival in the largest pre-clinical study conducted to date in this field, demonstrating success in sustaining kidney function in non-human primates for over two years.
“The results are unprecedented and signify a monumental step forward for achieving human compatibility.”
Professor Tatsuo Kawai, from Harvard Medical School, added: “This dataset demonstrates remarkable progress in editing the porcine genome to minimise hyperacute rejection, improve recipient compatibility and address the risk of viral transmission from donor to host.
“We anticipate that transplant outcomes in humans will be even more favourable, as these gene-edited organs are a better match for humans, as compared with non-human primates.”
In an accompanying editorial, one of the world’s foremost experts on the topic, Professor Muhammad Mohiuddin from University of Maryland Medical Centre in the US, said: “It is time for clinical translation of this vital technology, which has the potential to save lives that would otherwise be lost to the shortage of human organs.
“There is still much to be learnt from non-human, primate, preclinical models.
“But it will be clinical trials, enrolling people who have been excluded from all other hope of treatment, that will truly further our understanding of this remarkable procedure, and help to realise the potential of this technology.”
Figures from NHS Blood and Transplant show that 5,562 people are waiting for a kidney transplant in the UK, which is more than three quarters of all people waiting for any kind of transplant in the UK.
When a human receives an organ, tissue or cells from an animal it is known as a xenotransplant.
Pigs are the most promising donor animals due to the availability of pig, gene-editing technology, plus their size and similarities to human organs.
Overcoming the rejection of pig organs by the human immune system has been a complex challenge for more than four decades.
But gene-editing technology and new techniques to suppress the immune system have shown promise in several recent experiments.
Two humans have received pig heart transplants, the first, in 2022, was David Bennett who died two months after the surgery.
The second patient, a 58-year-old with end-stage heart disease, received his new heart on September 20.
University of Maryland Medical Centre in the US, which performed both of the pioneering heart surgeries, said the patient, Lawrence Faucette, “continues to recover and has commenced physical therapy”.
And, recently, scientists in the US, from NYU Langone Health, managed to transplant a genetically modified pig kidney into the body of a 58-year-old man who was brain dead.
The kidney functioned for about two months – the longest successful transplant of its kind.
