Heart failure & cardiomyopathies
Characterizing the Immune Response in Pig-to-Human Heart Xenografts Using a Multimodal Diagnostic System
Authors' conclusion
Multimodal phenotyping of pig-to-human heart xenografts revealed early signs of xenoimmune response, characterized by mild innate microvascular inflammation, endothelial activation, and a molecular signature characteristic of antibody-mediated rejection.
Study context
- Population
- Brain-dead human recipients of hearts from 10-gene-edited pigs
- Participants
- 2 heart xenografts
- Comparison
- Pig-to-human heart xenografts vs control pig hearts
- Xenograftsn = 2
- Outcome
- Xenoimmune response and injury by multimodal phenotyping (morphology, immunophenotyping, ultrastructure, automated multiplex immunofluorescence, gene expression)
- Follow-up
- 66 hours after reperfusion
Main finding
As reported in the abstract
- Both xenografts: endothelial activation and mild microvascular inflammation without capillary C4d deposition
- Immune infiltrates mainly CD15+ and CD68+ innate immune cells
- Ultrastructure: endothelial swelling with occasional intravascular leucocytes
- Deep learning-based multiplex immunofluorescence: microvascular inflammation primarily associated with CD15+ and CD68+ innate immune cells
- Increased expression of genes/pathways of monocyte/macrophage activation, neutrophil activation, interferon-gamma response, natural killer cell burden, endothelial activation, apoptosis and injury repair
- Phenotype absent in all control pig hearts, independent of ischemia/reperfusion injury and brain death
Original publication
Characterizing the Immune Response in Pig-to-Human Heart Xenografts Using a Multimodal Diagnostic System. Circulation. Published 2 October 2025. doi:10.
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