Trials of Xenotransplantation of Pig Organs into Humans Continue
Researchers have genetically engineered pigs to overcome the known barriers to transplantation of pig organs into humans, and have reached the stage of conducting transplants into terminally ill volunteers and brain dead individuals who donated their bodies to science. To learn by doing is really the only practical way by which the presently unknown problems are discovered. This trial of kidney transplantation ran for longer than prior efforts, and is a step on the path to producing a ready supply of non-human organs for transplantation, a technology that will compete with efforts to grow new organs on demands.
Surgeons have transplanted a genetically engineered pig kidney that continues to function well after 32 days in a man declared dead by neurologic criteria and maintained with a beating heart on ventilator support. This represents the longest period that a gene-edited pig kidney has functioned in a human. The first hurdle to overcome in xenotransplants is preventing so-called hyperacute rejection, which typically occurs just minutes after an animal organ is connected to the human circulatory system. By "knocking out" the gene that encodes the biomolecule known as alpha-gal - which has been identified as responsible for a rapid antibody-mediated rejection of pig organs by humans - immediate rejection has been avoided. Additionally, the pig's thymus gland, which is responsible for educating the immune system, was embedded underneath the outer layer of the kidney to stave off novel, delayed immune responses. The combination of modifications has been shown to prevent rejection of the organ while preserving kidney function.
To ensure the body's kidney function was sustained solely by the pig kidney, both of the transplant recipient's native kidneys were surgically removed. One pig kidney was then transplanted and started producing urine immediately without any signs of hyperacute rejection. During the observation phase, intensive care clinical staff maintained the decedent on support while the pig kidney's performance was monitored and sampled with weekly biopsies. 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.
The kidney and thymus gland used in this procedure were procured from a GalSafe pig, an animal engineered by Revivicor Inc., a subsidiary of United Therapeutics Corporation. In December 2020, the U.S. Food and Drug Administration (FDA) approved the GalSafe pig as a potential source for human therapeutics, as well as a food source for people with alpha-gal syndrome, a meat allergy caused by a tick bite. While previous genetically engineered pig organ transplants have incorporated up to 10 genetic modifications, this latest study shows that a single-gene knockout pig kidney can still perform optimally for at least 32 days without rejection.