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

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

Research output: Contribution to journalArticle

108 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5903-5910
Number of pages8
JournalBiomaterials
Volume31
Issue number22
DOIs
StatePublished - Aug 1 2010

Fingerprint

Tumor Microenvironment
Alginate
Chitosan
Scaffolds
Glioma
Tumors
Neoplasms
Cytology
Tissue culture
Vascular Tissue Neoplasms
Cellular Microenvironment
Blood vessels
Cell proliferation
Laminin
Matrix Metalloproteinases
Fibronectins
Cell culture
Heterografts
Design of experiments
Vascular Endothelial Growth Factor A

Keywords

  • Alginate
  • Chitosan
  • Glioma
  • Natural polymer
  • Scaffold
  • Tumor microenvironment

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Kievit, F. M., Florczyk, S. J., Leung, M. C., Veiseh, O., Park, J. O., Disis, M. L., & Zhang, M. (2010). Chitosan-alginate 3D scaffolds as a mimic of the glioma tumor microenvironment. Biomaterials, 31(22), 5903-5910. https://doi.org/10.1016/j.biomaterials.2010.03.062

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.

In: Biomaterials, Vol. 31, No. 22, 01.08.2010, p. 5903-5910.

Research output: Contribution to journalArticle

Kievit, FM, Florczyk, SJ, Leung, MC, Veiseh, O, Park, JO, Disis, ML & Zhang, M 2010, 'Chitosan-alginate 3D scaffolds as a mimic of the glioma tumor microenvironment', Biomaterials, vol. 31, no. 22, pp. 5903-5910. https://doi.org/10.1016/j.biomaterials.2010.03.062
Kievit, Forrest M. ; Florczyk, Stephen J. ; Leung, Matthew C. ; Veiseh, Omid ; Park, James O. ; Disis, Mary L. ; Zhang, Miqin. / Chitosan-alginate 3D scaffolds as a mimic of the glioma tumor microenvironment. In: Biomaterials. 2010 ; Vol. 31, No. 22. pp. 5903-5910.
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