Advances in Organ and Tissue Xenotransplantation.
Advances in genetic engineering of donor pigs and novel immunosuppression have moved xenotransplantation from preclinical models into the first human pig-organ transplants, though immune rejection, latent pathogen reactivation, and long-term survival remain unresolved challenges.
Background
Organ allotransplantation is constrained by a severe shortage of human donor organs, leaving many patients to die while waiting for a transplant. Xenotransplantation using organs from genetically modified pigs has re-emerged as a promising potential solution, driven by gene-editing technologies such as CRISPR-Cas9 that allow deletion of porcine xenoantigens and insertion of human transgenes.
Key recommendations
Pig organs are engineered with multiple genetic modifications, including knockout of carbohydrate antigens such as Galα1-3Gal and insertion of human complement-regulatory and other transgenes, to reduce hyperacute and acute rejection. Decades of pig-to-nonhuman-primate studies established the feasibility that preceded recent pig-to-human heart and kidney transplants in brain-dead and living recipients since 2022, supported by intensified immunosuppression and breeding of pathogen-controlled donor pigs.
Clinical implications
Despite encouraging early function of pig kidneys and hearts in humans, gene modification alone has not overcome all immunologic barriers, with T cell- and antibody-mediated rejection still occurring and porcine cytomegalovirus/roseolovirus reactivation reported. Persistent concerns about zoonotic infection, the need for refined immunosuppression, and the absence of documented long-term survival mean continued research and careful patient selection are essential before xenotransplantation becomes a routine therapy.
Category
Transplant
Source
Annu Rev Anim Biosci
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