Human liver tissue has been reconstructed in 3D at a cellular level, revealing how cirrhosis alters the organ’s internal structure compared with healthy tissue.
The 3D reconstructions capture the fine-scale microstructure of multiple liver lobes and show how scarring disrupts biological activity inside the organ.
Cirrhosis is extensive scarring of the liver caused by long-term damage from viral infection, metabolic disorders, certain medicines or alcohol misuse.
A healthy liver performs more than 500 essential functions, including detoxification, metabolism, digestion, nutrient storage, blood clotting and immune defence.
Kelly Stevens is professor of bioengineering at the UW School of Medicine and the UW College of Engineering, and a senior author of the research.
She said: “Our field has skimmed over a fact that could prevent this dream from becoming reality: We do not know what complex organs look like at a cellular level.
“We do not yet have the ‘blueprints’ of human organs to feed into bioprinters.
“This oversight is important because decades of studies have shown that the structure of human organs, particularly the organ-specific topology of its vasculature, is intimately connected to organ function.
“If the maps are not right, the organs produced will not be functional.”
The work was carried out by engineers and physicians at UW Medicine and the University of Washington, who developed what they describe as the Liver Map pipeline.
Tissue samples were taken from patients who had parts of their liver removed during cancer surgery or who underwent liver transplantation, including samples from cirrhotic livers.
The causes of cirrhosis varied across the samples.
Through the reconstructions, the researchers identified several structural changes linked to cirrhosis.
These included disrupted transport of metabolites in the sinusoidal zones of liver lobes, a reduction in specialised cells that help lower toxic ammonia levels, regression of central vein networks, disruption of artery networks and fragmentation of the bile network, which carries the fluid used to digest fats.
Taken together, the findings point to a broader shift in the liver’s vascular network, meaning the system of blood vessels that supports circulation within the organ.
The team also views the work as a step towards developing replacement organs.
Organ bioprinting is an emerging effort to use 3D printers to build living tissue layer by layer from cells and biomaterials to create organs or partial replacements for transplantation.
The researchers highlighted a key limitation.
The current imaging approach cannot yet capture the full depth of a human liver lobule, the hexagonal units that make up the organ, though they expect this to be addressed as the technology advances.
