What does a successful test of a pig-to-human kidney transplant mean?

A New York City surgeon successfully attached a porcine kidney to a human patient and observed the pinkish organs functioning normally for 54 hours. Although such a procedure is performed in non-human primates, it is the first time that a porcine kidney has been transplanted into the human body and has not been immediately rejected.

procedure, Announced at a press conference October 21 shows progress towards the goal of significantly expanding the supply of life-saving organs. Millions of people around the world are waiting for organ donations, many of which never come.

Details of the procedure have not yet been peer-reviewed or published in the journal, but “this is an important step,” said Megan Sykes, an immunologist at Columbia University who was not involved in the study. However, she says, patients waiting for their kidneys need to take more steps to easily get their kidneys from pigs.

Here are the answers to some of the basic questions about milestones:

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Why pig?

“It never solves the problem of organ shortages in human organs,” says John Scandling, a nephrologist at Stanford University who was not involved in the study. “There is a limit to the number of dead donor organs that can survive,” says living people donating too little.

In the United States, more than 100,000 people are on the national transplant waiting list, about 90 percent of whom need kidneys. However, in 2019, there were less than 40,000 transplants.About 17 people die every day While waiting for an organ, according to the Department of Health Resources.

Scientists have long sought to solve this deficiency by using animal organs, a field known as xenotransplantation. Pigs have emerged as the main focus of this study because pig organs are anatomically similar to human organs and animals can reproduce in a highly controlled manner.

However, simply transplanting other species of organs into a person causes the immune system to revolt in the presence of a large foreign body. When researchers attempted such experiments with non-human primates in the mid-20th century, scientists discovered that transplanted organs quickly turned black. “I was able to see the organs failing at the time because of the immediate reaction,” says Scandling. Its immediate reaction, called hyperacute rejection, is the first major obstacle for xenografts to stick together.

In recent decades, genetic engineering has overcome some of these challenges. Scientists have learned that the aggressive immune response seen after xenotransplantation in pigs is stimulated by antibodies that detect specific sugar molecules called alphagal that are scattered in the blood vessels of pigs.It’s the same sugar molecule that causes several Allergic reaction to lean meat (((SN: 7/30/18).

In the early 2000s, scientists devised a way to nullify the porcine gene that causes this sugar.Subsequent studies with the kidney Other organs Pigs with this gene disabled can be successfully transplanted into non-human primates, including baboons (SN: 12/5/18). But until now, testing of this type of transplant has not been successful in people.

What did the researchers do?

Performing such first surgery on a living person raises many ethical issues. However, in late September, a family of women who died of brain death but survived on a ventilator agreed to the surgery, according to Robert Montgomery, a surgeon at NYU Langone Health in New York City, who led the surgery team. She was removed from life support after surgery.

The woman was an organ donor, but her organs were not suitable for donation. “Want to [acknowledge] In deep sorrow, Montgomery said in deep sorrow how grateful he was to the deceased’s family for finding a way to help fulfill his desire to give a gift to humanity when his loved one died. ” .. In New York City.

Over two hours, Montgomery and his team carefully attached porcine kidneys genetically engineered to lack alphagal sugar into blood vessels in the patient’s upper limbs. The kidneys were kept outside the body so that the team could evaluate their function in real time. Pig thymus, which helps educate the immune system to recognize the kidneys as part of the body, has also been transplanted into organs to increase acceptance, Montgomery said. Drugs that suppress the immune system were also given.

Within minutes, the kidneys began to produce large amounts of urine, showing other signs of normal functioning. The team closely monitored the kidneys for 54 hours with no signs of refusal. “The porcine kidney acted like a human kidney transplant,” Montgomery said.

The research team stopped monitoring after 54 hours, following guidance from the ethics examiner.

How big is transplantation?

For scientists working on xenotransplantation, this news is welcomed and important, but not so surprising.

“We were all pretty confident that there would be no hyperacute rejection,” says Parsia Vagefi, a transplant surgeon at the UT Southwestern Medical Center in Dallas. He states that the porcine kidneys used in this procedure persisted in non-human primates for over a year.

“This is a proof of principle,” says Vagefi. “But from a scientific point of view, I didn’t actually move the needle.” for example.

Peter Cowan, an immunoscientist at the University of Melbourne, Australia, agrees. “This is perfectly predictable, but nevertheless important evidence to support the transition of porcine to human kidney xenotransplantation to clinical trials.”

What’s next for this kind of transplant?

Surviving 54 hours is an important first step, but “no one needs a kidney for three days,” says Vagefi. Before pig-raised organs become mainstream, researchers need to demonstrate that organs can withstand attacks from other players in the immune system and last for months or years in the human body.

For example, over time, T cells, a type of white blood cell, may recognize the transplanted organ as a foreign body and attack it. Immunosuppressive drugs can help mitigate this type of reaction, although the side effects of such drugs, such as susceptibility to infections, can be significant.

Inclusion of pig thymus, which helps make immune system cells and antibodies with the kidneys, may help reduce this long-term rejection, is a surgeon, immunologist, and non-human primate at Columbia University. Kazuhiko Yamada, who has been working on this method for decades. “It’s like an educated teacher [the immune system] Don’t attack your kidneys. “

Researchers will also have to show that such transplants are long-term safe in order to get approval from the US Food and Drug Administration, Yamada says. For example, pig organs may contain retroviruses that are sleeping in genes.Some researchers use the gene editing technology CRISPR Remove those viruses To potentially improve safety (SN: August 10, 2017).

Pigs may also be able to donate other organs such as the heart and liver, but various organs present their own challenges.

“We’ve been working on this for 20 years,” says Yamada, but now it seems like “you can turn the final corner and see the finish line.” But he says it’s not yet known how long it will take for people in need of kidneys to easily get kidneys from pigs.

Is it ethical to raise pigs to harvest organs?

The future, in which millions of pigs are potentially raised to harvest organs for humans, raises serious ethical issues. “Pigs are not spare parts and should not be used that way just because they are too self-centered for humans to donate their bodies to patients who are anxious for organ transplants,” said the animal in the tissue. People for the Ethical Treatment of (PETA) said. In the statement..

Proponents of xenotransplantation argue that the potential benefits of significantly expanding organ supply are worth the potential harm done to pigs.

“Almost half of the patients waiting for a transplant get sick or die before they get the transplant,” said Montgomery, a NYU surgeon. “The traditional paradigm that someone has to die for someone to live never keeps up with the ever-increasing incidence of organ failure.”