US surgeons transplant genetically modified pig kidneys into man

US surgeons have transplanted kidneys from a genetically modified pig into a man who was left brain-dead by a motorbike accident.

The operation at the University of Alabama at Birmingham was the latest step towards bringing xenotransplantation — replacing failed human organs with those from animals — into clinical practice.

The UAB announcement follows the first successful transplant of a gene-edited pig’s heart into a living patient at the University of Maryland School of Medicine earlier this month. “The patient is continuing to recover with no signs of rejection of his heart,” the Maryland team said on Wednesday.

Xenotransplants have been on the medical research agenda for several decades, as a way to ease the worldwide shortage of transplant organs from human donors. But advances in genetics and immunology have only recently brought the technology to a point at which regulators will consider its use.

“It is curative for an end-stage disease. If you don’t fix this problem, the patient is going to die,” said Jayme Locke, lead surgeon for the UAB project. “The opportunity to have an organ waiting for the person who needs it is remarkable to think about.”

Revivicor, a Maryland-based biotechnology company that is part of the United Therapeutics group, developed the pigs used for both heart and kidney transplants. Its scientists made 10 genetic changes in the animals — inactivating four porcine genes and adding six human genes — to reduce the risk of rejection by the recipient’s immune system and help the organ grow in a human body.

While the University of Maryland team transferred a pig’s heart into a living patient, the UAB surgeons operated on a brain-dead 57-year-old man, Jim Parsons.

Locke said Parsons was a “pre-clinical human model” used to demonstrate that the pig’s kidneys would function successfully for a few days after his own kidneys were removed. In the event, they purified his blood, with no signs of rejection, until Parsons’s life support had to be switched off because his body was failing from other effects of his motorbike accident.

The pig came from a herd living in a pathogen-free facility close to the UAB campus. Before surgery, the team carried out a crossmatch compatibility test to confirm that the gene-edited kidney and its recipient were a good tissue match, as they would with a human organ.

After the transfer “the kidney turned beautiful and pink”, Locke said, “and within 23 minutes, it started making urine”. The kidneys remained viable until the experiment, which took place last September, ended after 77 hours. Details are published in the American Journal of Transplantation.

Although Parsons had been a registered organ donor, his organs turned out to be unsuitable for transplantation. Instead, his family agreed that UAB could keep his body functioning on a ventilator during the experiment. The procedure had been approved by the university’s ethics committee.

At the end of this year, the UAB team hopes to receive regulatory approval to start a phase 1 clinical trial in living patients who need new kidneys but cannot find human donors. The trial is likely to involve 10 to 20 people. If it goes well, several hundred volunteers would be needed for a phase 2 trial.

If xenotransplants eventually become routine, there will be no problem supplying tens of thousands of pigs a year from secure pathogen-free facilities, said David Ayares, Revivicor’s chief scientist. “These young, fresh animals, which can be grown to size to suit the patient, will be the solution to the organ shortage crisis,” he said.