American surgeons have successfully transplanted a genetically modified pig kidney that continues to function well 32 days after the transplant. The prowess of this xenograft offers hope to compensate for the lack of available grafts.
Xenografts: hope in the face of the shortage of available organs
The global organ shortage is a major health problem. To overcome this shortage, xenotransplantation, which consists of transplanting an organ from a donor whose biological species is different from that of the recipient, is a promising solution.
For anatomical reasons (morphological and physiological similarities), porcine organs have been favored but until now the immunological barriers between the species led to a phenomenon of hyperacute rejection and the loss of the graft. But advances in biotechnology today allow incredible progress.
Pig kidney continues to function 32 days after transplant
Several pig organ transplants have been performed in the past with more or less obvious success rates. But the announcement from the NYU Langone Hospital team in New York is unprecedented. The genetically modified proc kidney has been working properly for 32 days, the longest period for such an experiment in humans.
To prevent hyperacute rejection of the transplanted organ, the gene that codes for the biomolecule known as alpha-gal – which has been identified as responsible for the rapid rejection of organs of pig by humans. Additionally, the porcine thymus gland, which is responsible for educating the immune system, has been embedded under the outer layer of the kidney to prevent further delayed immune responses. The combination of these modifications has been shown to prevent organ rejection while preserving kidney function.
This operation was performed on a brain-dead man. To ensure that the kidney function of the body was supported solely by the pig kidney, both of the recipient’s kidneys were removed. A pig kidney was then transplanted and started producing urine immediately without any signs of hyperacute rejection.
A “simpler” procedure for kidney xenografts
Previous genetically modified pig organ transplants have incorporated up to 10 genetic modifications, but this study shows that just one allows the kidney to function optimally for at least a month. This might make the process easier (at least for the kidney transplant).
The kidney and thymus used in this procedure come from a GalSafe TM pig, an animal genetically modified by the firm Revivicor, Inc. In December 2020, the American authorities (Food and Drug Administration) approved this animal as a potential source of therapeutics humans as well as a food source for people with alpha-gal syndrome, a meat allergy caused by a tick bite.
A big step towards a new source of organs
“There simply aren’t enough organs available for everyone who needs them.“said Dr. Montgomery, who himself received a heart transplant.”Too many people are dying because of the lack of available organs, and I am convinced that xenotransplantation is a viable way to change that.“says Dr. Montgomery.
And for the surgeon, this discovery is a big step towards a new source of organs. “We believe that using a pig already deemed safe by the FDA in combination with what we have found in our xenotransplantation research so far brings us closer to the clinical trial phase.“, said Dr. Montgomery. “We know this has the potential to save thousands of lives, but we want to ensure the utmost safety and care as we move forward.“.
