Extracellular Matrix Functionalization and Huh-7.5 Cell Coculture Promote the Hepatic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells in a 3D ICC Hydrogel Scaffold
Abstract
In this study, we constructed a microporous hydrogel scaffold with hexagonally packed interconnected cavities and extracellular matrix (ECM)-functionalized interior surface, and systematically investigated the hepatic differentiation of human adipose-derived mesenchymal stem cells (hAD-MSCs) under the influence of three key factors: three-dimensional (3D) geometry, ECM presence, and coculture with hepatocyte-derived cell line. Results confirmed that (i) hepatic differentiation of hAD-MSC is more efficient in a 3D microporous scaffold than in 2D monolayer culture; (ii) the presence of both ECM components (fibronectin and collagen-I) in the scaffold is superior to collagen-I only, highlighting the importance of fibronectin; and (iii) coculture with Huh-7.5 hepatocyte-derived cells promoted liver-specific functions of the hAD-MSC-derived hepatocytes. The optimized differentiation process only took 21 days to complete, a time length that is shorter or at least comparable to previous reports, and more importantly, yielded an albumin production more than 10-fold higher than conventional 2D culture. Our approach of optimizing hAD-MSC hepatic differentiation could provide a potential solution to the challenges such as hepatocyte transplantation or the establishment of human physiologically relevant liver models in vitro .
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A combination of collagen I and fibronectin compared to collagen I alone functionalized within a PEG gel enhanced hepatic differentiation from human mesenchymal stem cells.
“A combination of collagen I and fibronectin compared to collagen I alone functionalized within a PEG gel enhanced hepatic differentiation from human mesenchymal stem cells98.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [98]
Some collagen-based culture methods rely on coculture with supporting cells, which introduces undefined components into the organoid culture.
“However, some collagen-based culture methods rely on coculture with supporting cells98, which introduces undefined components into the organoid culture.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [98]
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Towards organoid culture without Matrigel
Kozlowski, M. T., Crook, C. J., & Ku, H. T. (2021) · Communications Biology · doi:10.1038/s42003-021-02910-8 · Cited by 409 · see citing works
- Authors
- Wang, Y., Lee, J.-H., Shirahama, H., Seo, J., Glenn, J. S., & Cho, N.-J.
- Affiliations
- Nanyang Technological University (SG)
- Stanford Medicine (US)
- Corresponding author
- Cho, Nam-Joon
- Venue
- ACS Biomaterials Science & Engineering
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-10-28
- Volume
- 2
- Issue
- 12
- Pages
- 2255-2265
- ISSN
- 2373-9878 (ISSN-L)
- OpenAlex
- W2535139328
- Cited by
- 21
- References
- 51
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 1
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Biomaterials Science & Engineering (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation Singapore (NRF-CRP10-2012-07, NRF-NRFF2011-01)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- hepatic differentiation, human adipose-derived mesenchymal stem cells, fibronectin, type I collagen, hydrogel scaffolds, 3D cell culture, albumin synthesis, liver tissue engineering, hepatocyte transplantation
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