Scientists have created never-before-seen 3D reconstructions of human liver tissue at a cellular level. This detailed work, performed by a team of UW Medicine and University of Washington engineers and physicians, captures the spatial microstructure of multiple lobes of the liver.
The Liver's Vital Role and the Impact of Cirrhosis
The human liver performs over 500 essential functions, including detoxification, metabolism regulation, digestion aid, nutrient storage, protein production for blood clotting, and infection resistance.
The new 3D reconstructions reveal how cirrhosis, characterized by extensive scarring, profoundly alters the liver's intricate architecture and its biological activities.
Introducing the Liver Map Pipeline
The research team refers to their groundbreaking methodology as the Liver Map pipeline, detailed in Science Advances.
Future applications of this approach could lead to improved treatments for cirrhosis and inform the development of replacement organs.
"Understanding cellular-level structure is crucial for the future of bioprinting artificial organs. Current efforts often lack the detailed 'blueprints' of human organs needed for functional bioprinting, as organ structure, particularly vasculature, is intimately linked to function."
— Kelly Stevens, Professor of Bioengineering, UW School of Medicine and UW College of Engineering
Organ bioprinting involves using 3D printers to construct living tissues layer by layer. This process aims to create functional organs or partial replacements for transplantation, utilizing living cells, biomaterials, and techniques to establish blood flow.
Technological Advancements and Key Researchers
The creation of these 3D liver reconstructions benefited significantly from recent innovations in optics, imaging technologies, computational analysis, and chemistry, moving beyond traditional 2D microscopic views.
The lead scientists on this project included Wesley B. Fabyan, Chelsea L. Fortin, and Dorice L. Goune. Senior authors were Kelly Stevens, Rotonya M. Carr (professor of medicine), and Raymond S. W. Yeung (cancer surgeon and professor of surgery).
Insights from Cirrhotic Liver Samples
Tissue samples for the study were obtained from patients undergoing cancer surgery or liver transplants, with some specimens coming from cirrhotic livers. Cirrhosis typically results from persistent damage due to viral infections, metabolic disorders, medications, or alcohol abuse.
The 3D reconstructions vividly showed that cirrhosis impacts liver architecture in several critical ways:
- Dysregulation of metabolite transport in the sinusoidal zone.
- Reduction in specialized liver cells that help lower ammonia levels.
- Regression of central vein networks.
- Disruption of artery networks.
- Fragmentation of the bile transport network.
These observations collectively suggest a significant shift in the cirrhotic liver's vascular network.
Limitations and Future Directions
A current limitation of the Liver Map pipeline is its inability to capture the entire depth of a human liver lobule. The scientists aim to address this in future advancements.
This pioneering research received funding from multiple sources, including various National Institutes of Health grants, the National Science Foundation, and the Howard Hughes Medical Institute.