Three‐dimensional coculture of primary hepatocytes and stellate cells in silk scaffold improves hepatic morphology and functionality in vitro
Abstract
A vigorous in vitro model of liver that could recapitulate hepatic phenotype and functionality in vivo would exclusively improve the efficiency of bioartificial liver, drug discovery, or even transplantation therapy. Owing to the indispensable role of three-dimensional (3D) microenvironment in supporting viability and function of hepatocytes in vitro, much effort recently has been focused on improving reproducibility and standardization of primary hepatocyte cultures with a paradigm shift to 3D culture system, In the present study, an improved 3D coculture system of hepatocytes was established in which rat primary hepatocytes were cocultured with hepatic stellate cells in silk porous scaffolds. Silk scaffolds with incorporated extracellular matrix provided a suitable microenvironment for maintaining the viability, morphology and gene expression of the primary hepatocyte in vitro. The presence of stromal cells promoted primary hepatocyte to generate cellular aggregates with well-organized 3D architecture after 3 days of coculture in vitro. These aggregates exhibited proper morphology similar to liver tissue in vivo. Consistent with their phenotypic appearance, well-maintained functionality of hepatocytes was also observed in the cocultures, where albumin secretion/expression, urea synthesis as well as messenger ribonucleic acid expression of multiple cytochrome Ps (CYPs) enzymes increased significantly compared to either the 3D monocultures or monolayer cultures. Additionally,…
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Cell-cell and cell-matrix interactions are important for improving hepatic functions in liver models.
“The development of hepatocyte sandwich cultures (SCs), co-cultures with non-parenchymal cells and even more advanced 3-dimensional culturing techniques has revealed the importance of cell-cell and cell-matrix interactions for improving hepatic functions in liver models (Bachmann et al., 2015[2]; Duval et al., 2017[9]; Wei et al., 2018[45]).”
From Optimization of extracellular matrix for primary human hepatocyte cultures using mixed collagen-matrigel matrices (2023) · cites this paper as Wei et al., 2018[45]
Cites
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Long-Term Culture and Coculture of Primary Rat and Human Hepatocytes
Shulman, M., & Nahmias, Y. (2012) · Methods in Molecular Biology · doi:10.1007/978-1-62703-125-7_17 · Cited by 117 · see citing works
Three-dimensional co-culture of hepatocytes and stellate cells
Abu-Absi, S. F., Hansen, L. K., & Hu, W.-S. (2004) · Cytotechnology · doi:10.1007/s10616-004-7996-6 · Cited by 92 · see citing works
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Engineering Liver Microtissues for Disease Modeling and Regenerative Medicine
Huang, D. (., Gibeley, S. B., Xu, C., Xiao, Y., Celik, O., Ginsberg, H. N., & Leong, K. W. (2020) · Advanced Functional Materials · doi:10.1002/adfm.201909553 · Cited by 65 · see citing works
Seidemann, L., Prinz, S., Scherbel, J.-C., Götz, C., Seehofer, D., & Damm, G. (2023) · IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund · doi:10.17179/excli2022-5459 · Cited by 3 · see citing works
“…cultures (SCs), co-cultures with non-parenchymal cells and even more advanced 3-dimensional culturing techniques has revealed the importance of cell- cell and cell-matrix interactions for improving hepatic functions in liver models (Bachmann et al., 2015; Duval et al., 2017; Wei et al., 2018).”
- Authors
- Wei, G., Wang, J., Lv, Q., Liu, M., Xu, H., Zhang, H., Jin, L., Yu, J., & Wang, X.
- Affiliations
- Dalian Medical University (CN)
- Soochow University (CN)
- Corresponding author
- Wang, Xiuli
- Venue
- Journal of Biomedical Materials Research Part A
- Publisher
- Wiley
- Published
- 2018-04-30
- Volume
- 106
- Issue
- 8
- Pages
- 2171-2180
- ISSN
- 1549-3296 (ISSN-L)
- 1552-4965
- OpenAlex
- W2795530700
- Cited by
- 32
- References
- 4
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 1
- FWCI
- 1.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Biomedical Materials Research Part A (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31771068, 31470952, 81173125)
- Natural Science Foundation of Liaoning Province (2014023003)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Silk-based biomaterials and applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- silk scaffolds, primary hepatocytes, hepatic stellate cells, extracellular matrix, drug metabolism, cytochrome P450, albumin secretion, urea synthesis, bioartificial liver, rat hepatocytes
- MeSH terms
- Albumins, Animals, Cell Survival, Cells, Cultured, Gene Expression Regulation, Liver, Male, Urea, Rats, Sprague-Dawley, Coculture Techniques, Hepatocytes, Silk, Cell Proliferation, Tissue Scaffolds, Hepatic Stellate Cells
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