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In a first, genetically edited pig kidney is transplanted into human

Procedure marks milestone in quest to provide more organs to patients in need

By Mass General Brigham Communications

In a first-of-its-kind medical procedure, Harvard Medical School physician-scientists at Massachusetts General Hospital have transplanted a genetically edited pig kidney into a human.

While many unknowns remain about the viability of the newly transplanted organ and the patient’s long-term health, the procedure — made possible in part by scientific advances by researchers at HMS — marks a major milestone in the quest to alleviate critical shortages of human kidneys for patients with end-stage kidney failure.

In a first, genetically edited pig kidney is transplanted into human
Surgeons transplant the pig kidney. “It was truly the most beautiful kidney I have ever seen,” said team co-lead Tatsuo Kawai (center). Credit: Massachusetts General Hospital

The patient, 62-year-old Richard (Rick) Slayman of Weymouth, Mass., received the kidney in a four-hour surgery on March 16. He has type 2 diabetes and high blood pressure, the most common causes of chronic kidney disease.

Slayman had previously received a human kidney transplant, but that kidney showed signs of failure after five years, sending him back to dialysis with end-stage kidney failure and requiring regular hospital visits for management of dialysis complications.

“The success of this transplant is the culmination of efforts by thousands of scientists and physicians over several decades. We are privileged to have played a significant role in this milestone,” said Tatsuo Kawai, HMS professor of surgery and director of the Legorreta Center for Clinical Transplant Tolerance at Mass General, who helped lead the transplant team and also conducted Slayman’s first kidney transplant in 2018.

“Our hope is that this transplant approach will offer a lifeline to millions of patients worldwide who are suffering from kidney failure,” he said.

Addressing a critical need

Researchers have been exploring the transplantation of organs or tissues from other animals, known as xenotransplantation, as a solution to a worldwide shortage of donated organs. Transplantations of pig hearts into living patients and of pig kidneys into brain-dead recipients have made recent headlines.

According to the United Network for Organ Sharing, more than 100,000 people in the U.S. are awaiting an organ for transplant, and 17 people die each day waiting for an organ. Kidneys are the most common organs needed, according to literature published in the Journal of the American Society of Nephrology.

Of the estimated 36 million people in the U.S. affected by chronic kidney disease, some 800,000 have end-stage kidney disease or kidney failure, a terminal condition that requires either a new kidney or painful, prolonged dialysis sessions that filter waste from the blood and can last several hours at a time, several times a week.

Safely transplanting organs from animals into humans requires multiple steps to minimize the risk of the recipient’s immune system rejecting the new organ — also a concern with human organ transplants — and to prevent infection and other complications.

“If it were easy, we’d be doing it by now, but it’s not,” said Joren Madsen, the Paul S. Russell/Warner-Lambert Professor of Surgery at HMS and director of the MGH Transplant Center. “The barrier to pig xenotransplantation is formidable. The good news is we’ve been able to overcome that barrier.”

Scientific advances

The first step involved genetically modifying the pig organs to be more compatible with humans. The kidney used in the new surgery was modified using the gene-editing technology CRISPR-Cas9 to:

  • Remove certain pig genes that produce sugars with antibodies our immune systems react to.
  • Add certain human genes to improve the kidney’s compatibility with humans.
  • Inactivate viruses present in all pig genomes, known as porcine endogenous retroviruses, in the donor pig to eliminate risk of infection in the recipient.

In all, the kidney had 69 genomic edits.

The modified kidney was provided by eGenesis, a xenotransplantation therapy company co-founded by Wyss Institute Core Faculty Member and Harvard Medical School geneticist George Church and former Wyss and HMS postdoctoral fellow Luhan Yang. Over the past five years, Mass General and eGenesis have conducted extensive research, with findings published in Nature in Oct. 2023, based on earlier genome-editing advances made at the Wyss and HMS in 2015.

Slayman, the patient, also received new monoclonal antibody drugs specifically designed to suppress immune reactions against pig tissue.

The drugs were provided without cost by two pharmaceutical companies.

“This collaborative nature of academia and industry is crucial for advancements such as the one we’re sharing today,” said Leonardo Riella, the HMS Harold and Ellen Danser Associate Professor of Surgery and medical director for kidney transplantation at Mass General.

The organs and immunosuppressant drugs were extensively tested in animal models to ensure the team developed an optimal protocol for application in humans, Madsen said.

The kidney “immediately pinked up”

As soon as the surgical team — led by Riella, Kawai, and Nahel Elias, HMS assistant professor of surgery, interim chief of transplant surgery, and surgical director for kidney transplantation at Mass General — finished connecting the kidney, the new organ “immediately pinked up,” said Winfred Williams, HMS associate professor of medicine at Mass General and Slayman’s nephrologist.

“They held up the ureter and it was producing urine,” he said. “Applause broke out in the OR. It was quite an amazing experience.”

Nearly one week after the surgery, Slayman is recovering well and is expected to be discharged soon, according to the Mass General team.

“The real hero today is the patient, Mr. Slayman, as the success of this pioneering surgery, once deemed unimaginable, would not have been possible without his courage and willingness to embark on a journey into uncharted medical territory,” said Madsen.

Cautious optimism

The longer-term results of the transplant are not yet clear.

“There are so many unknowns,” said Riella. “This is the first time we’re doing it.”

The surgery will be considered a success if Slayman doesn’t need to go back on dialysis, according to a Mass General FAQ. The team hopes the pig kidney improves Slayman’s health and buys him time to perhaps receive another donated human kidney.

“We still don’t know how many years this kidney can survive, but based on our preclinical research, we are aiming at years — more than two years,” said Kawai.

Slayman was approved for the experimental procedure under a single FDA Expanded Access Protocol, or EAP, often called a compassionate-use protocol. These are granted to a single patient or group of patients with serious, life-threatening illnesses or conditions to gain access to experimental treatments or trials when no comparable treatment options or therapies exist.

Riella led the team in applying for the EAP. The FDA rigorously reviewed it before issuing its approval in late February.

Fully understanding the effectiveness of porcine kidney transplantation requires not only more time but also more patients.

“This is a compassionate-use, one-patient study,” said Williams. “You’d want to take this to a larger clinical trial to make sure this is a safe modality for transplantation. A multi-center-based trial would go a long way toward establishing the research efficacy for this model.”

It could turn out, for instance, that organs from pigs require even more genetic edits for optimal results.

For now, hopes are running high about the potential of kidney xenotransplantation to one day save lives and to improve quality of life by reducing the need for kidney dialysis.

“Our hope is that dialysis will become obsolete,” said Riella. “We feel strongly that xenotransplantation is a reasonable option either as a bridge [on the way to receiving a human kidney] or hopefully in the future as a permanent treatment.”

“At MGH alone, there are over 1,400 patients on the waiting list for a kidney transplant,” he said. “Some of these patients will unfortunately die or get too sick to be transplanted due to the long waiting time on dialysis. I am firmly convinced that xenotransplantation represents a promising solution to the organ shortage crisis.”

Eye on health disparities

The team also has an eye toward ensuring that xenotransplantation helps reduce, rather than perpetuate or exacerbate, health disparities associated with organ failure and transplantation.

Unequal access to kidney transplants for ethnic minority patients is one of the more intractable problems in the field, and national policy initiatives have had only limited success in 30 years, said Williams.

“An abundant supply of organs resulting from this technological advance may go far to finally achieve health equity and offer the best solution to kidney failure — a well-functioning kidney — to all patients in need,” Williams said.

Williams said he commends Slayman, who is Black, “for his courageousness in becoming a trailblazer in the field of transplantation.”

When Williams and the transplant team first suggested a pig kidney transplant, carefully explaining the pros and cons of the procedure, “I saw it not only as a way to help me, but a way to provide hope for the thousands of people who need a transplant to survive,” Slayman said in a statement.

Cost is another factor. The expense associated with Slayman’s transplant as a first-of-its-kind procedure is “enormous,” said Williams, making it inaccessible to most patients; but if the surgery eventually becomes routine, that cost should diminish, he said.

History of success

Mass General Brigham has a rich history in organ transplant innovation. HMS surgeons at Brigham and Women’s Hospital performed the first successful human organ transplant — also of a kidney — in 1954. Today’s Mass General transplant clinicians and surgeons have nearly 30 years of combined experience with xenotransplantation research.

Slayman’s team included physicians, surgeons, scientists, anesthesiologists, and nurses, said Elias.

“The tireless commitment of our clinicians, researchers, and scientists to improving the lives of our transplant patients — both current and future — is at the very heart and soul of academic medicine and what it means to work and provide care at Mass General Brigham,” said David F. M. Brown, president of academic medical centers at MGB. “We are so thankful to the incredible staff throughout our hospitals who helped make this surgery a success and to the patient for his bravery and courage.”

Adapted from a Mass General Brigham news release and press conference.

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