Pig-to-Baboon Heart Transplant Survives Nearly Nine Months

Researchers from the Cardiac Xenotransplantation Program at the University of Maryland have shown that a genetically-modified pig heart can last for up to nine months in non-human primates, a significant advancement in the field that could one day support heart transplantation in humans.

Their publication, “Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months,” in the journal Xenotransplantation, follows news of the first-ever pig-to-human heart transplant, performed in January by the same Maryland-based team.

For many individuals with heart failure, an organ transplant is the only life-saving treatment option. Yet, due to a limited supply of human hearts available for transplant, for some patients the procedure does not occur quickly enough.

Every year adults and children in the United States pass away while on the wait list to receive a heart from a human organ donor.

To reduce the extent of this supply-demand mismatch, researchers have had a long-standing interest in identifying alternative sources of organs.

In recent years, pigs have shown the greatest promise among non-human organ donors.

However, there are a number of challenges associated with transplanting pig organs into humans, including immunologic rejection, differences in human and animal physiology, and the risk of transmitting animal-borne viruses and other disease-causing pathogens.

In this case, the research team introduced a total of six genetic modifications into the donor pigs to increase the probability that the pig organs could work in primates.

The genetic changes were intended to reduce the magnitude of the immune response against the pig organ, blood clotting that could threaten the life of the graft, and abnormal organ growth sometimes seen when pig hearts are transplanted into primates.

The research was an extension upon previous work performed by the team, which involved the transplant of pig hearts with three genetic modifications.

In addition to receiving the genetically-modified organs, the baboons in the study were infused with an immunosuppressive agent targeting the protein CD40. CD40 is normally involved in the production of antibody, an important source of graft rejection in xenotransplantation.

Notably, the CD40-based immunosuppressive therapy used in the study is not currently FDA-approved for use in humans, although a similar therapy targeting CD40 is currently being explored in multiple clinical trials.

The baboons did not require additional medications to prevent graft rejection, control blood pressure, or regulate changes in the size of the heart, problems that appeared in past experiments.

According to the research team, the data “demonstrate[d] that selective “multi-gene” modifications improve cardiac xenograft survival significantly and may be foundational for paving the way to bridge transplantation in humans.”

“Multigene xenografts may immediately reduce certain patients’ morbidity and mortality as a bridge to allotransplantation, who would otherwise die waiting for a heart,” the researchers concluded.

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Mohiuddin MM, Goerlich CE, Singh AK, et al. (2022) Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months. Xenotransplantation, 29(3): e12744.