Spatial biology of liver transplantation: Mapping injury, immunity, and repair in the allograft

The liver is a highly spatially organized organ in which microanatomy underpins metabolism, immune regulation, and regenerative capacity. In liver transplantation, spatially defined processes, including ischemia reperfusion injury (IRI), alloimmune activation, and disease recurrence critically shape graft function and long-term outcomes. However, conventional bulk and single-cell transcriptomics and proteomics approaches lack the ability to resolve these events within their native tissue context. Recent advances in spatial transcriptomic and proteomic technologies enable high-resolution mapping of cellular interactions within healthy tissue, providing new insight into the microenvironmental niches that drive graft injury and repair. This review summarizes current spatial omics platforms, including sequencing-based, imaging-based, and microdissection approaches, with emphasis on technical and analytic considerations relevant to transplantation. It synthesizes emerging applications in key transplant settings, including IRI, machine perfusion-mediated graft reconditioning, alloimmune injury, chronic remodelling, and recurrent liver disease. Spatial studies demonstrate that liver graft injury arises within discrete immune-stromal-parenchymal niches that influence progression toward recovery or chronic dysfunction. Translation into clinical practice will require longitudinal sampling and harmonized workflows, and will be significantly enhanced by integration with artificial intelligence-driven analytics. Ultimately, spatially resolved molecular signatures may improve donor assessment, enable early risk stratification, and guide precision interventions, advancing a biology-informed approach to liver transplantation.