Earlier this year, there were reports of the first experimental xenotransplantation: a human patient with heart disease received a heart from a pig that had been genetically engineered to avoid rejection. While initially successful, the experiment ended two months later when the transplant failed, leading to the death of the patient. At the time, the team did not provide any details about what went wrong. But this week saw the publication of a research paper that explains the weeks leading up to and the weeks after transplant preparation.
Crucially, this includes eventual failure of the transplant, which resulted from the death of many muscle cells in the transplanted heart. But the cause of that death is unclear, and typical signs of rejection by the immune system were not present. So, we have to wait a bit to understand what went wrong.
a solid start
Overall, the paper paints a picture of organ recipient David Bennett as a patient who was on the verge of death at the time of the transplant. He was an obvious candidate for a heart transplant and was kept alive only through the use of a device that helped oxygenate his blood outside his body. But the patient had what the researchers refer to as “poor adherence to treatment,” which led him to refuse human heart transplants from four different transplant programs. At that point, he and his family agreed to participate in the experimental xenotransplant program.
The pig that served as the heart donor came from a population that has been extensively genetically engineered to limit the possibility of rejection by the human immune system. The line was also free of a specific virus that inserts itself into the pig genome (porcine endogenous retrovirus C, or pERV-C) and was raised in conditions that should limit pathogen exposure. The animal was also screened for virus before transplantation, and the patient was subsequently screened for pig pathogens.
After the transplant, the patient’s new heart performed well, displaying a normal rhythm between 70 and 90 beats per minute. Most significantly, more than half of the blood filling the left ventricle of the transplanted heart was diverted into the circulatory system with each contraction; This was just above 10 percent in the diseased heart that he had replaced.
About two weeks after the transplant, Bennett began to experience abdominal pain and weight loss, which eventually resulted in his weight exceeding 20 kg (40 lb). He was placed on a feeding tube, and an exploratory laparoscopy showed possible signs of an infection that was resolving, but no action was deemed to be required. A little later, screening turned up a possible infection with the pig version of cytomegalovirus; The human version of this virus causes issues such as pneumonia and mononucleosis. This was controlled with antiviral treatment.
While weight loss was an obvious concern, five weeks after the transplant, there were no signs of rejection, and the heart was still functioning.