Researchers have claimed a major step forward in the field of organ transplantation after a monkey survived for more than two years with a genetically engineered pig kidney.
The work is the latest to emerge from the US biotech company eGenesis and Harvard Medical School, where scientists see genetically altered pigs as a potential solution to the global shortage of donors for patients with organ failure.
Dr Michael Curtis, the chief executive of eGenesis, said the “extraordinary milestone” provided hope for the approach and “may pave the way for better outcomes for countless individuals in need of lifesaving organ transplants”.
Scientists have spent decades working out whether animal organs could ever work properly and safely in humans without them being rejected by the patient’s immune system, but the challenges have proved immense.
For the latest trial, researchers used a gene-editing tool called Crispr to alter genes in Yucatan miniature pigs before transplanting their kidneys into macaques. The modifications altered genes to prevent organ rejection and remove pig viruses that could potentially be activated in recipients.
Writing in the journal Nature, the scientists describe how 21 monkeys fared after their kidneys were removed and a single genetically modified pig kidney was implanted. Monkeys typically survived only 24 days when the kidneys were edited to disable three genes that trigger immune rejection. But when the scientists added seven human genes that reduce blood clotting, inflammation and other immune reactions, the monkeys survived seven times longer, typically for 176 days.
When combined with treatment to suppress the immune system, the researchers report that one monkey survived for more than two years – 758 days – with the transplanted organ.
Curtis said the long-term survival of at least some of the monkeys had put eGenesis on course to satisfy the US Food and Drug Administration requirement to see at least 12 months’ survival in animals before the team can launch a clinical trial in humans.
“We are well on our way there,” Curtis said. “There simply aren’t enough kidneys to go around. In our opinion it’s the only near-term viable solution.”
The team uses Yucatan miniature pigs as donors because at maturity their kidneys are roughly the same size of those in the adult human. In the monkey trial, the kidneys were transplanted at two to three months when the organs were much smaller.
Prof Tatsuo Kawai, an author on the study at Harvard Medical School, said the scientists expected the modified pig organs to perform better in humans than monkeys because “they are a better match”.
Two humans have so far received pig heart transplants. The first, David Bennett, died two months after surgery in 2022. The second, 58-year-old Lawrence Faucette, who had end-stage heart disease, received a new heart on 20 September this year and is in recovery.
Prof Muhammad Mohiuddin, at the University of Maryland School of Medicine, who was involved in the pioneering heart transplants, said genetically modified pig organs should move into human trials.
“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,” he wrote in an accompanying editorial.
“There is still much to be learned 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.”
Prof Dusko Ilic, at King’s College London, called the work a “groundbreaking achievement”, but said: “There is still a long way to go before this strategy could be used in clinical trials.”
Meanwhile, a separate study has suggested that pioneering transplant therapy could reduce organ rejection rates and avoid the need for patients to take life-long anti-rejection drugs, according to research.
Scientists at the University of Pittsburgh School of Medicine found that giving patients the organ donor’s dendritic cells could “teach” the recipient’s immune system to accept the new organ.
Dendritic cells help the body’s immune system launch a response to potential threats. They also help it tolerate harmless components instead of attacking them.
In a phase 1 clinical trial, published in the journal Science Translational Medicine, 13 patients were given a single infusion of the organ donor’s dendriditic cells a week before their liver transplant. The researchers followed them for a year alongside 40 liver transplant patients who received the usual regimen of anti-rejection immunosuppressant drugs and found no differences between the two groups in organ rejection rates.
