xenotransplants

Xenotransplantation is the transplantation of living cells, tissues, or organs between different species. The most studied sources are pigs and non-human primates, with pig organs favored for size, breeding practicality, and the potential for precise genetic modification. Xenografts may involve whole organs such as heart or kidney, as well as cellular products like islets or other tissues.

Biological barriers to successful xenotransplantation include rapid immune rejection and potential transmission of animal pathogens. Hyperacute rejection occurs when the recipient's immune system recognizes donor carbohydrate antigens (for example the alpha-gal epitope), leading to immediate graft loss. Researchers have used genetic engineering to address this by knocking out problematic genes (such as GTKO, which eliminates alpha-gal) and adding human genes that regulate complement, coagulation, and immune responses (for example human CD46, CD55, and other regulatory proteins). Additional modifications aim to improve organ compatibility and reduce the need for lifelong immunosuppression. Advances in gene editing, notably CRISPR/Cas9, have accelerated donor animal development. Immunosuppressive regimens remain integral but carry infection and cancer risks. There are also concerns about zoonotic transmission of pathogens, including porcine endogenous retroviruses.

Clinical progress has included long-standing studies in non-human primates and the initiation of regulated human trials in the 2020s. A landmark event was the transplantation of a genetically modified pig heart into a patient in 2022, which demonstrated feasibility but highlighted challenges in durability and infection risk. Research continues with other organ types and cell-based approaches, and some programs are pursuing pig islets and other tissues for metabolic and regulatory indications.

Ethical and regulatory considerations cover animal welfare, informed consent, equitable access, and public health implications. Oversight bodies in different countries assess safety, manufacturing standards, and long-term monitoring. Xenotransplantation remains experimental in most settings and is subject to ongoing evaluation as technology and safety data evolve.