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Three-dimensional liver-derived extracellular matrix hydrogel promotes liver organoids function.
Mona Saheli1, Mohammadmajid Sepantafar2,3, Behshad Pournasr3
1Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Journal of Cellular Biochemistry
|December 17, 2017
Summary
This study shows that a novel 3D liver extracellular matrix hydrogel (LEMgel) significantly enhances the function of liver organoids. These engineered liver organoids show improved physiological activity for potential tissue engineering applications.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Cell Biology
Background:
- Extracellular matrix (ECM)-derived biomaterials offer tunable microenvironments for tissue engineering.
- Liver-derived ECM hydrogel (LEMgel) fabrication is crucial for developing functional liver organoids.
Purpose of the Study:
- To assess if 3D liver ECM hydrogel (LEMgel) promotes physiological function in self-organized liver organoids.
- To optimize LEMgel production preserving key ECM components.
Main Methods:
- Optimized decellularization of sheep liver ECM to create LEMgel, characterized by SEM.
- Fabricated 3D liver organoids using hepatocarcinoma, mesenchymal, and endothelial cells within LEMgel.
- Analyzed organoid gene expression, protein secretion, urea production, and enzyme activity.
Main Results:
- LEMgel exhibited optimal viscoelasticity and a pore size of 382 ± 71 µm.
- Liver organoids in 3D LEMgel (LEMgel organoids) expressed key liver markers (ALB, CYP3A4) and showed epithelial phenotype.
- LEMgel organoids demonstrated significantly upregulated liver-specific gene transcripts and enhanced albumin (ALB), alpha-1-antitrypsin (AAT) secretion, urea production, and CYP3A4 activity compared to controls.
Conclusions:
- 3D LEMgel significantly enhances the functional activity of self-organized liver organoids.
- Novel 3D LEMgel organoids show promise for liver tissue engineering, drug discovery, toxicology, and bio-artificial liver development.
