Expectations from the first pig-to-human kidney transplant

According to CNN, the four-hour surgery was performed on March 16 at Massachusetts General Hospital, which also performed the world's first kidney transplant in 1954.

Patient Rick Slayman (62 years old) was previously diagnosed with end-stage renal disease. He is recovering well and is expected to be discharged soon.

In a statement on March 21, doctors said they expected Mr. Slayman’s new kidney to function well for many years, but also acknowledged that there are many unknowns in animal-to-human organ transplants.

Mr. Slayman has been a patient in the hospital’s transplant program for 11 years. He received a donor kidney in 2018 while suffering from diabetes and high blood pressure. However, the function of the new kidney has been declining over the next five years, forcing Mr. Slayman to return to dialysis in 2023.

Last year, Mr. Slayman was diagnosed with end-stage kidney disease and doctors recommended he try pig kidneys.

“For me, it not only helped me but also brought hope to thousands of people who need transplants to survive,” Mr. Slayman shared.

The medical community considers the transplant surgery on March 16 to mark an important medical milestone.

“This is finally happening after years of work and collaboration,” said Dr. Parsia Vagefi, chief of transplant surgery at UT Southwestern Medical Center in Dallas. “It’s really a big step forward and a great time for transplantation.”

Dr. Tatsuo Kawai, director of the Legorreta Clinical Transplant Tolerance Center and the surgeon who performed the surgery, said the pig kidneys were identical in size to human kidneys.

When the transplant team sewed the pig kidney into Mr. Slayman's body, the blood vessels reconnected and the kidney immediately “turned pink again and began producing urine.”

“It was truly the most beautiful kidney I had ever seen,” Dr. Kawai, one of 15 people involved in the operation, said at a press conference.

Currently, the demand for transplant organs far exceeds the number available. Every day, 17 people in the United States die while waiting for an organ. Kidneys are the organ in the shortest supply. According to the Organ Procurement and Transplantation Network, about 27,000 kidneys will be transplanted in the country in 2023, but nearly 89,000 people remain on the waiting list.

Experts say xenotransplants – a term that refers to the act of transplanting organs from animals into humans – play a very important role in solving the current shortage of organs for patients.

“This could also be a potential breakthrough in solving one of the most difficult problems we face,” said Dr. Winfred Williams, deputy chief of nephrology at Massachusetts General Hospital. “It could be an opportunity to give ethnic minority patients equal access to kidney transplants.”

This is the third pig organ transplant into a living person. The first two were pig heart transplants into living people. Both patients died within weeks of receiving the organs.

The researchers said that while the latest surgery marks an important step forward, more research is needed. Ideally, a large study conducted at multiple hospitals would be needed to better understand the effectiveness of pig kidney transplants.

Xenotransplantation is a boon for patients like Slayman, who have great difficulty with dialysis, said Dr. Leonardo Riella, medical director of kidney transplantation at Massachusetts General Hospital. Vascular disease, diabetes, and high blood pressure make patients more susceptible to blood clots during dialysis, complicating treatment. To remove the clots, Slayman must undergo between three and 40 procedures.

“At one point, he said he didn’t think he was going to continue,” Dr. Williams said, adding that at that point, he began exploring unconventional options and came up with the idea of ​​using pig organs for Mr. Slayman.

Milestones gradually taking shape

The transplanted kidney came from a pig that eGenesis Bio had genetically modified to be more compatible with humans. Other companies are also working to create pig tissues and organs suitable for xenotransplantation.

Since the 1600s, scientists have experimented with extracting blood and skin from this animal for human use.

Although pig kidneys are very similar to human kidneys, finding a way to prevent the human immune system from rejecting them is not easy, researchers say.

“The human immune system reacts very aggressively to pig organs, much more so than to human organs,” said Dr. Joren Madsen, director of the Center for General Transplantation. Madsen pointed out that if a recipient of a pig kidney transplant were given the same anti-rejection drugs that are given to patients receiving human kidney transplants, the new pig organ would be rejected and turn black within minutes.

The latest surgery made three important advances and finally made xenotransplantation a reality.

First, eGenesis used CRISPR-Cas9 technology to make 69 precise edits to the pig’s DNA to prevent the human body from recognizing the pig’s kidneys as foreign and rejecting them. They removed three regulatory genes normally expressed on the surface of pig cells that human antibodies can recognize and attack. They also used gene editing to disable pig retroviruses that could become activated and infect humans.

Second, pharmaceutical companies can create special monoclonal antibodies specifically designed to prevent pig organ rejection.

Finally, the researchers were able to test pig organs in non-human animal models to develop the best procedures for applying the technology to humans.

“This successful process heralds a new era in medicine, one in which we remove barriers to organ supply and realize the goal that no patient should die while waiting for an organ transplant,” said Dr. Michael Curtis, CEO of eGenesis.