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Chitosan–alginate 3D scaffolds as a mimic of the glioma tumor microenvironment
Open accessAbstract
Despite recent advances in the understanding of its cell biology, glioma remains highly lethal. Development of effective therapies requires a cost-effective in vitro tumor model that more accurately resembles the in vivo tumor microenvironment as standard two-dimensional (2D) tissue culture conditions do so poorly. Here we report on the use of a three-dimensional (3D) chitosan-alginate (CA) scaffold to serve as an extracellular matrix that promotes the conversion of cultured cancer cells to a more malignant in vivo-like phenotype. Human U-87 MG and U-118 MG glioma cells and rat C6 glioma cells were chosen for the study. In vitro tumor cell proliferation and secretion of factors that promote tumor malignancy, including VEGF, MMP-2, fibronectin, and laminin, were assessed. The scaffolds pre-cultured with U-87 MG and C6 cells were then implanted into nude mice to evaluate tumor growth and blood vessel recruitment compared to the standard 2D cell culture and 3D Matrigel matrix xenograft controls. Our results indicate that while the behavior of C6 cells showed minimal differences due to their highly malignant and invasive nature, U-87 MG and U-118 MG cells exhibited notably higher malignancy when cultured in CA scaffolds. CA scaffolds provide a 3D microenvironment for glioma cells that is more representative of the in vivo tumor, thus can serve as a more effective platform for development and study of anticancer therapeutics. This unique CA scaffold platform may offer a valuable alternative strategy to the time-consuming and costly animal studies for a wide variety of experimental designs.
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Self-citation
Metadata
- Authors
- Kievit, F. M., Florczyk, S. J., Leung, M. C., Veiseh, O., Park, J. O., Disis, M. L., & Zhang, M.
- Affiliations
- University of Washington (US)
- Corresponding author
- Zhang, Miqin
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 31
- Issue
- 22
- Pages
- 5903-5910
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC2883048
- OpenAlex
- W2078576156
- Cited by
- 209
- References
- 29
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 3 · 2023: 19 · 2022: 14 · 2021: 14 · 2020: 21 · 2019: 12 · 2018: 14 · 2017: 10 · 2016: 17 · 2015: 17 · 2014: 14 · 2013: 22 · 2012: 7
- FWCI
- 6.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation
- National Institutes of Health
- National Cancer Institute (U01CA141539, R01CA134213, T32CA138312, R01CA119408)
- National Institute of Biomedical Imaging and Bioengineering (R01EB006043)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Keywords
- glioma, 3D tumor models, tumor microenvironment, extracellular matrix, U87 cells, C6 glioma cells, vascular endothelial growth factor, MMP-2, fibronectin, laminin, tumor angiogenesis, tumor growth, xenografts, anticancer drug screening
- MeSH terms
- Alginates, Animals, Cell Transformation, Neoplastic, Glioma, Hexuronic Acids, Humans, Male, Mice, Nude, Neovascularization, Pathologic, Glucuronic Acid, Cell Line, Tumor, Chitosan, Mice, Rats, Tissue Scaffolds
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