Xenotransplantation literature update March 2023-November 2023.
Across the March 2023 to November 2023 period, kidney xenotransplantation literature continued to advance, with pig-to-human decedent and preclinical studies refining understanding of immune responses while confirming that antibody-mediated rejection remains the principal obstacle.
Background
Xenotransplantation using genetically modified pigs is being pursued to address the chronic shortage of human kidneys for transplantation. Gene-editing of donor pigs to delete carbohydrate xenoantigens and express human regulatory proteins has enabled prolonged graft survival in pig-to-non-human-primate models and supported initial pig-to-human studies in brain-dead decedent recipients.
Key recommendations
Multimodal phenotyping of pig-to-human kidney xenografts indicates that, despite favourable short-term outcomes and absence of hyperacute injury, antibody-mediated rejection may still occur, characterized by microvascular inflammation, endothelial activation, and infiltration by innate immune cells including macrophages and natural killer cells. This evidence supports targeting the humoral arm of rejection and underscores the need for careful immunological characterization, pathogen monitoring, and continued study in decedent models before expanded clinical application.
Clinical implications
The accumulating literature suggests that while gene modification has largely overcome hyperacute rejection and pig kidneys can restore renal function in human recipients, durable success will require improved control of accelerated and antibody-mediated rejection, attention to physiological differences between species, and management of potential zoonotic infection. These considerations will shape eligibility criteria and trial design as xenotransplantation moves toward systematic clinical evaluation.
Category
Transplant
Source
Xenotransplantation
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