Gene-edited pig kidney works for 32 days in brain-dead man

A genetically modified pig kidney transplanted into a brain-dead man on life support has exhibited regular functioning for over a month, showing no signs of rejection or infection.
Mrigakshi Dixit
Representational picture.
Representational picture.

Akarawut Lohacharoenvanich/iStock 

A new milestone in animal-to-human organ transplants in the United States has been achieved. 

A gene-edited pig kidney implanted into a brain-dead man on life support has been functioning normally for over a month with no signs of rejection or infection.  

This is the "longest period" that a pig kidney has worked within a human body. Surgeons from the New York University Langone Transplant Institute performed the procedure on July 14, 2023. 

This significant medical breakthrough holds promise in addressing future challenges related to organ shortages.

“This work demonstrates a pig kidney—with only one genetic modification and without experimental medications or devices—can replace the function of a human kidney for at least 32 days without being rejected,” said Dr Robert Montgomery, who led this surgery, in an official release.  

The operation was performed on Maurice Miller, who passed away unexpectedly at 57 years old. Subsequently, his family contributed his body to medical science research.

Several modifications were made for successful xenotransplantation

Nonetheless, achieving animal-to-human transplantation, referred to as xenotransplantation, required several modifications.

The first challenge faced by the surgical team was to avert hyperacute rejection, a phenomenon that occurs within minutes of connecting a foreign organ to the human circulatory system.

To address this issue, the team removed a gene that produces alpha-gal, a biomolecule responsible for "rapid antibody-mediated rejection of pig organs by humans".

Additionally, the surgeons added a pig's thymus gland, vital in immunity generation, beneath the outer layer of the kidney to prevent delayed immunological reactions. 

These alterations in combination enabled the body to evade organ rejection and restored regular kidney function.

The official statement noted that the pig kidney began producing urine shortly after the surgery was done, with no indications of hyperacute rejection.

Biopsies are conducted every week to assess the overall functioning of the pig kidney. “Levels of creatinine, a bodily waste product found in the blood and an indicator of kidney function, were in the optimal range during the length of the study, and there was no evidence on biopsy of rejection,” added the release. 

Gene-edited pig kidney works for 32 days in brain-dead man
Jeffrey Stern, MD, (left) and Robert Montgomery, MD, DPhil, prepare to implant a genetically modified pig kidney into the abdomen.

Kidney obtained from engineered pig 

While previous pig organ transplants modified as many as 10 genes, this recent procedure centers on the removal of a single gene in the pig kidney.

“We’ve now gathered more evidence to show that, at least in kidneys, just eliminating the gene that triggers a hyperacute rejection may be enough along with clinically approved immunosuppressive drugs to successfully manage the transplant in a human for optimal performance—potentially in the long-term,” said Dr. Montgomery.

The researchers will continue to monitor the transplanted kidney's overall performance until mid-September 2023.

For this surgery, the kidney and thymus gland were procured from a GalSafeTM pig, engineered by Revivicor, Inc.

The use of GalSafe pig was officially approved by the US Food and Drug Administration (FDA) in December 2020. Its applications include human therapeutics and as a dietary source for those suffering from alpha-gal syndrome, a meat allergy caused by a tick bite.

The development is not yet published in a scientific journal.

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