Researchers have developed unprecedented 3D reconstructions of human liver tissue at the cellular level. These detailed models capture the spatial microstructure across multiple lobes of the liver, a vital organ that performs over 500 essential functions. These tasks include detoxifying harmful substances, regulating metabolism, supporting digestion, storing nutrients, producing blood clotting proteins, and bolstering infection resistance.
The Liver Map Pipeline
The innovative Liver Map pipeline enables these visualizations, as detailed in a study published in the February 18 issue of Science Advances. This approach uncovers how cirrhosis, characterized by extensive liver scarring, disrupts the organ’s intricate architecture and impairs its biological processes. Future applications could improve cirrhosis treatments to preserve or restore liver function and guide the development of engineered replacement organs.
Blueprint for Bioprinted Organs
Organ bioprinting aims to construct functional tissues layer by layer using living cells, biomaterials, and techniques to establish blood flow and promote cell renewal. Kelly Stevens, professor of bioengineering at the UW School of Medicine and UW College of Engineering, emphasizes the need for precise cellular blueprints. A senior author on the study and leader in artificial organ development, Stevens states, “Our field has skimmed over a fact that could prevent this dream from becoming reality: We don’t know what complex organs look like at a cellular level.”
She adds, “We don’t 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 [arrangement of blood vessels] is intimately connected to organ function.” Stevens warns, “If the maps aren’t right, the organs produced will not be functional.”
Advanced Imaging Technologies
Recent advances in optics, imaging, computational analysis, and chemistry have elevated tissue visualization beyond traditional 2D microscopy. “Scientists are now equipped with an enhanced imaging toolkit that is better at elucidating tissue structure and its disease-associated alterations,” the study notes.
Key Researchers and Samples
Lead scientists Wesley B. Fabyan, Chelsea L. Fortin, and Dorice L. Goune from the Department of Bioengineering and UW Medicine Institute for Stem Cell and Regenerative Medicine spearheaded the project. Senior authors include Stevens, Rotonya M. Carr, professor of medicine and head of the Division of Gastroenterology, and Raymond S. W. Yeung, UW Medicine and Fred Hutch cancer surgeon and professor of surgery.
Samples originated from patients undergoing liver cancer surgery or transplants, with consent for research use. Some specimens exhibited cirrhosis from causes like viral infections, metabolic disorders, medications, or alcohol abuse.
Cirrhosis Effects on Liver Architecture
The 3D models reveal cirrhosis-induced changes, including disrupted metabolite transport in sinusoidal zones, reduced specialized cells that detoxify ammonia, regressed central vein networks, fragmented artery systems, and bile transport disruptions. These alterations signal a broader shift in the liver’s vascular and biliary networks, dysregulating its architecture across scales.
Limitations and Future Prospects
Current imaging cannot yet capture the full depth of liver lobules, the organ’s hexagonal units, though ongoing Liver Map advancements aim to overcome this. The research received support from the National Institutes of Health, National Science Foundation, Howard Hughes Medical Institute, and other programs. DOI: 10.1126/sciadv.adz2299
