Chitosan–alginate 3D scaffolds as a mimic of the glioma tumor microenvironment

Kievit, Forrest M.; Florczyk, Stephen J.; Leung, Matthew C.; Veiseh, Omid; Park, James O.; Disis, Mary L.; Zhang, Miqin

doi:10.1016/j.biomaterials.2010.03.062

Cited by 209Hydrogels: synthesis, properties, applications3D Printing in Biomedical ResearchGlioma Diagnosis and Treatment

Chitosan–alginate 3D scaffolds as a mimic of the glioma tumor microenvironment

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Kievit, Forrest M., Florczyk, Stephen J., Leung, Matthew C., Veiseh, Omid, Park, James O., Disis, Mary L., Zhang, Miqin·2010·Biomaterials

DOI 10.1016/j.biomaterials.2010.03.062PMC PMC2883048

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Abstract

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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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: Kievit, Forrest M.
Florczyk, Stephen J.
Leung, Matthew C.
Park, James O.
Disis, Mary L.
Zhang, Miqin
Venue: Biomaterials
Publisher: Elsevier BV
Published: 2010-08
Volume: 31
Issue: 22
Pages: 5903-5910
ISSN: 0142-9612 (ISSN-L)
DOI: 10.1016/j.biomaterials.2010.03.062
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
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: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Health Sciences › Medicine › Genetics › 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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Chitosan–alginate 3D scaffolds as a mimic of the glioma tumor microenvironment

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