In an experiment paving the way for clinical trials, two pig kidneys produced urine for 77 hours after transplantation into the body of a man who was brain dead
20 January 2022
Two pig kidneys genetically engineered to prevent rejection by the immune system have been transplanted into a man who was brain dead as a first step towards treating patients. The kidneys weren’t rejected during the 77 hours that the experiment, carried out in the US, lasted.
“This game-changing moment [is] a major milestone in the field of xenotransplantation, which is arguably the best solution to the organ shortage crisis,” surgeon Jayme Locke at the University of Alabama at Birmingham said in a statement. The aim of the study is to pave the way for a clinical trial, which Locke hopes will get under way later this year.
The experiment took place on 30 September, but the details were revealed in a paper published today. The kidneys came from the same line of genetically modified pigs as the heart transplanted into David Bennett on 7 January. While Bennett got the pig heart because there were no other options for him, the kidney transplant was done as an initial safety test only.
The recipient, Jim Parsons, was injured during a motorcycle race. He was a registered organ donor, but none of his organs was suitable for transplantation. His family gave permission for his body to be kept alive on a ventilator so the study could be done. His own kidneys were removed and replaced with the genetically engineered pig kidneys.
“As a family, we had no doubt that this is what Jim would have wanted,” his ex-wife Julie O’Hara told a press briefing, standing alongside other family members.
Locke told the briefing that, while the idea of testing therapies in brain-dead people has been proposed before, her team is the first to do it. The Parsons model, as her team has decided to call it, could be valuable where animal testing isn’t sufficient, she said.
Pig organs cannot normally be transplanted into people because they are rejected by the human immune system, even if people are given immunosuppressant drugs. But the pigs created by US firm Revivicor have been genetically modified to prevent rejection.
Four genes have been switched off, including some that code for the proteins that provoke the immune response in humans. The pigs also have six added human genes.
This work was made possible by the development of the CRISPR gene-editing technique, said Locke. “With that, the field of xenotransplantation has exploded,” she said.
The pig kidneys weren’t rejected during the 77-hour experiment. “Within 23 minutes, it began to make urine,” said Locke, referring to the first of the two pig kidneys transplanted. “It’s a remarkable achievement. We had a beautiful pink kidney, not one that turned black from hyperacute rejection.”
However, while the kidneys produced urine, they didn’t remove a substance called creatinine from the blood, a key measure of normal kidney function. The team isn’t sure why this was the case, but it could be related to Parsons’s condition.
One potential issue is that pigs have a lower blood pressure than people, meaning the blood vessels in pig kidneys might be damaged by the higher blood pressure after transplantation. But the team saw no indication of any problems.
Another concern is that virus genes lurking in the genomes of pigs might be able to infect people, but the team found no sign of this. However, at least one other company working on creating pigs suitable for transplants is deleting all the viral genes to ensure this cannot happen.
Locke told the briefing that kidney transplantation is the cure for chronic kidney disease, but that most people die before they can receive one. There are around 100,000 people on the waiting list for transplants in the US, but fewer than 25,000 transplants are done each year.
“The need still far exceeds supply,” she said. “We need a radical solution.”
Journal reference: American Journal of Transplantation, DOI: 10.1111/ajt.16930
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