Surgeons in New York have successfully attached a kidney grown on a genetically engineered pig to a human patient and found the organ to be functioning normally, a scientific breakthrough that could one day produce a vast new supply of organs for them. critically ill patients.
Although many questions remain unanswered about the long-term consequences of the transplant, which involved a brain-dead patient followed for only 54 hours, experts in the field have said the procedure represents a milestone.
“We need to know more about organ longevity,” said Dr Dorry Segev, professor of transplant surgery at the Johns Hopkins School of Medicine who was not involved in the research. Nonetheless, he said: “It’s a huge breakthrough. This is a big, big problem.
Researchers have long sought to grow organs in pigs suitable for transplantation into humans. A constant flow of organs – which could eventually include hearts, lungs and livers – would offer a lifeline to the more than 100,000 Americans currently on transplant waiting lists, including the 90,240 who need of a kidney. Twelve people on waiting lists die every day.
An even greater number of Americans with kidney failure – more than half a million – depend on grueling dialysis treatments to survive. Largely because of the scarcity of human organs, the vast majority of dialysis patients are not eligible for transplants, which are reserved for people most likely to thrive after the procedure.
The operation, performed at NYU Langone Health, was first reported by USA Today on Tuesday. The research has not yet been peer reviewed or published in a medical journal.
The transplanted kidney was obtained from a pig genetically engineered to grow an organ unlikely to be rejected by the human body. In a close approximation of an actual transplant procedure, the kidney was attached to a person who had suffered brain death and was kept on a ventilator.
The kidney, attached to the blood vessels in the upper leg outside the abdomen, began to function normally, producing urine and creatinine waste “almost immediately,” according to Dr. Robert Montgomery, director of the NYU Langone Transplant Institute, which performed the procedure in September.
Although the organ has not been implanted in the body, problems with so-called xenotransplants – from animals like primates and pigs – usually occur at the interface of the human blood supply and organ, where human blood circulates through porcine vessels, the experts said.
The fact that the organ is working outside the body is a strong indication that it will work in the body, said Dr Montgomery.
“It was better than we expected, I think,” he said. “It looked like any transplant I have ever done from a living donor. Many kidneys of people who have died do not work right away and take days or weeks to start. It worked immediately.
Last year, 39,717 residents of the United States received organ transplants, the majority of them – 23,401 – receiving kidneys, according to the United Network for Organ Sharing, a nonprofit that coordinates the country’s organ procurement efforts.
Genetically modified pigs “could potentially be a sustainable and renewable source of organs – the sun and the wind of organ availability,” said Dr Montgomery.
Reactions to the news among transplant experts ranged from cautious optimism to wild outpouring, though all agreed that the procedure represented a sea change. The prospect of raising pigs to harvest their organs for humans is sure to raise questions about animal welfare and exploitation, although around 100 million pigs are already killed in the United States each. year to feed.
While some surgeons have speculated that it may be a few months before kidneys from genetically modified pigs are transplanted into living humans, others have said there is still a lot of work to be done. .
“This is truly a leading edge translational surgery and transplant that is on the verge of being able to be done in living humans,” said Dr Amy Friedman, former transplant surgeon and chief medical officer of LiveOnNY, the organ procurement organization for the greater New York City area.
The group was involved in the selection and identification of the brain dead patient receiving the experimental procedure. The patient was a registered organ donor, and because the organs were not suitable for transplantation, the patient’s family agreed to allow research to test the experimental transplant procedure.
Dr Friedman said she is also considering using hearts, livers and other organs grown in pigs. “It’s really mind-boggling to think of how many transplants we could offer,” she said, adding: “You have to raise the pigs, of course.”
Other experts were more reserved, saying they wanted to see if the results were reproducible and review the data collected by NYU Langone.
“There is no doubt that this is a feat, in that it is difficult to do and you have to overcome a lot of obstacles,” said Dr. Jay A. Fishman, Associate Director from the Massachusetts General Hospital Transplant Center.
“Whether this particular study advances the field will depend on what data they’ve collected and shared, or whether it’s a step just to show they can do it,” said Dr. Fishman. He urged humility “about what we know”.
There are still many hurdles to overcome before organs from genetically modified pigs can be used on living humans, said Dr David Klassen, chief medical officer of the United Network for Organ Sharing.
While he called the surgery a “watershed moment,” he warned that long-term organ rejection occurs even when the donor’s kidney is well adapted and “even when you are not trying to cross the barriers of the organs. species “.
The kidney has functions in addition to removing toxins from the blood. And there are concerns about pig viruses infecting recipients, said Dr Klassen: “It’s a complicated area, and to imagine that we know all the things that are going to happen and all the problems that are going to arise is naive.
Xenotransplantation, the process of grafting or transplanting organs or tissues between different species, has a long history. Efforts to use animal blood and skin in humans date back hundreds of years.
In the 1960s, kidneys from chimpanzees were transplanted into a small number of human patients. Most died soon after; the longest lifespan of a patient was nine months. In 1983, a baboon heart was transplanted into a baby girl known as Baby Faye. She died 20 days later.
Pigs offered advantages over primates for organ harvesting: they are easier to rear, mature faster, and reach adult human size in six months. Pig heart valves are commonly transplanted into humans and some diabetic patients have received pig pancreas cells. Pig skin has also been used as a temporary graft for burn patients.
The combination of two new technologies – gene editing and cloning – has produced genetically modified pork organs. Pig hearts and kidneys have been successfully transplanted into monkeys and baboons, but safety concerns have prevented their use in humans.
“So far, the field has been stuck at the preclinical primate stage, as moving from a primate to a living human is seen as a big leap,” Dr. Montgomery said.
The kidney used in the new procedure was obtained by removing a pig gene that encodes a sugar molecule that elicits an aggressive human rejection response. Pork has been genetically modified by Revivicor and approved by the Food and Drug Administration for use as a source of human therapy.
Dr Montgomery and his team also transplanted the pig’s thymus, a gland involved in the immune system, in an attempt to prevent immune reactions to the kidney.
After attaching the kidney to the blood vessels in the upper leg, surgeons covered it with a protective shield so that they could observe it and take tissue samples during the 54-hour study period. . Urine and creatinine levels were normal, Dr Montgomery and colleagues found, and no sign of rejection was detected for more than two days of observation.
“There did not appear to be any incompatibility between the pig kidney and the human that would render it inoperative,” said Dr Montgomery. “There was no immediate rejection of the kidney.”
Long-term prospects are still unknown, he admitted. But “it allowed us to answer a very important question: is there something going to happen when we go from a primate to a human that is going to be disastrous? “