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Longitudinal multiomics profiling of extracorporeal cross-circulation with pig liver xenografts in human decedents | Nature Medicine
Extracorporeal liver cross-circulation (ELC) using gene-edited porcine liver xenografts offers a potential bridge therapy for liver failure. We previously performed five ELC procedures in four brain-dead human decedents, during which the recipients developed severe thrombocytopenia. The porcine liver xenografts maintained their parenchymal structure, with immune cell infiltration and detectable IgM deposition on endothelial cells. Here, to investigate the underlying host–xenograft interactions, we performed longitudinal proteomic, lipidomic and metabolomic profiling of 64 blood samples, alongside spatial transcriptomics and histology of 25 porcine liver xenograft and 3 native human liver biopsies. Spatial transcriptomic analysis revealed progressive infiltration of human immune cells (predominantly inflammatory macrophages and neutrophils) in the xenografts, concurrent with the loss of porcine Kupffer-like macrophages and T cells. Distinct human and porcine complement dynamics were obs
