What to Know About a Xenotransplant Heart

A xenotransplant heart is an organ transplanted from an animal into a human. This procedure is a significant area of medical research, driven by the potential to provide a new source of organs for people with end-stage heart failure. The ability to source organs from animals could fundamentally change how heart failure is treated, offering hope to many who currently have limited options. This prospect fuels the scientific effort and public interest in using an organ from one species to replace a failing one in another.

The Critical Demand for Alternative Hearts

The pursuit of animal-to-human heart transplantation is fueled by a severe shortage of human donor organs. Thousands of individuals are on waiting lists, but the number of available hearts falls drastically short of the need. This disparity means many patients experience a decline in health while waiting for a compatible match that may never become available.

Current treatments have significant limitations. Mechanical devices like left ventricular assist devices (LVADs) are not a permanent cure and risk complications like blood clots and infections. Human-to-human transplants (allografts) are the current standard, but they require the recipient to take powerful immunosuppressant drugs for life to prevent organ rejection. These medications carry their own risks, including increased susceptibility to infections and other long-term health issues.

Engineering Hearts from Animal Sources

Preparing an animal heart for a human recipient involves genetic engineering, with pigs being the primary source. Pigs are chosen for their anatomical similarities to humans, as their hearts are a comparable size and function. They also have a short gestation period and produce large litters, allowing for efficient breeding. Using pigs also avoids some of the ethical concerns associated with using primates.

To make a pig heart suitable, scientists perform multiple genetic modifications to prevent hyperacute rejection, an immediate immune attack. Using technologies like CRISPR, they “knock out” specific pig genes that produce sugars, like alpha-gal, which the human body recognizes as foreign. Removing these molecular triggers is the first step to prevent rejection.

Scientists also “knock in” or add human genes to the pig’s DNA to make the heart appear less foreign. Human genes that regulate the immune response and blood clotting are inserted to improve compatibility. These additions help control inflammation and prevent blood clots, which are significant post-transplant risks.

The genetically modified pigs are raised in biosecure, pathogen-free environments to minimize the risk of transmitting animal-borne diseases. The animals’ health is monitored from birth to ensure they are free of viruses or other microorganisms that could pose a threat to the human recipient.

Landmark Procedures and Evolving Outcomes

Early xenotransplantation attempts provided foundational knowledge despite not being successful long-term. A noted case was “Baby Fae” in 1984, an infant who received a baboon heart and survived for 21 days. The procedure showed a cross-species organ could function temporarily in a human, highlighting the immunological barriers that needed to be overcome.

Recently, the field has progressed with genetically engineered pig hearts. In 2022 and 2023, surgeons at the University of Maryland School of Medicine performed two such transplants. The first patient, David Bennett, survived for two months, and the second, Lawrence Faucette, lived for nearly six weeks. These procedures showed that a modified pig heart could function in a human without immediate hyperacute rejection.

Researchers gathered invaluable data from these cases. In Mr. Bennett’s case, analysis suggested a porcine cytomegalovirus in the donor heart may have contributed to its failure, leading to more sensitive screening protocols for the second transplant. These experiences showed that managing the immune response and issues like organ swelling and infection remain complex challenges.

Overcoming Biological and Ethical Hurdles

The human immune system remains a barrier to long-term success. After preventing hyperacute rejection, the body can mount other attacks. Acute cellular rejection, mediated by T-cells, can occur weeks after surgery and requires management with immunosuppressive drugs. A slower form of rejection can also damage the heart’s blood vessels over time, leading to organ failure.

A concern unique to xenotransplantation is xenozoonosis, the transmission of diseases from animals to humans. Although donor pigs are raised in sterile conditions, dormant porcine viruses like porcine endogenous retroviruses (PERVs) could become active in a human. Scientists are working to screen for and edit out these viral genes, but the risk of cross-species infection remains a public health consideration.

The practice also raises ethical questions. The welfare of the genetically modified animals used as organ sources is a primary concern. Other debates involve ensuring equitable access to this therapy if it becomes widely available. Obtaining informed consent is also complex, as patients agree to an experimental procedure with uncertain long-term outcomes and risks.