Proliferation and enrichment of CD133(+) glioblastoma cancer stem cells on 3D chitosan-alginate scaffolds

Forrest M Kievit; Stephen J Florczyk; Matthew C Leung; Kui Wang; Jennifer D Wu; John R Silber; Richard G Ellenbogen; Jerry S H Lee; Miqin Zhang

doi:10.1016/j.biomaterials.2014.07.037

Proliferation and enrichment of CD133(+) glioblastoma cancer stem cells on 3D chitosan-alginate scaffolds

Biomaterials. 2014 Nov;35(33):9137-43. doi: 10.1016/j.biomaterials.2014.07.037. Epub 2014 Aug 7.

Authors

Forrest M Kievit¹, Stephen J Florczyk², Matthew C Leung², Kui Wang², Jennifer D Wu³, John R Silber¹, Richard G Ellenbogen⁴, Jerry S H Lee⁵, Miqin Zhang⁶

Affiliations

¹ Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA.
² Department of Materials Science & Engineering, University of Washington, Seattle, WA 98195, USA.
³ Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
⁴ Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA; Department of Radiology, University of Washington, Seattle, WA 98195, USA.
⁵ Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Center for Strategic Scientific Initiatives, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁶ Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA; Department of Materials Science & Engineering, University of Washington, Seattle, WA 98195, USA. Electronic address: mzhang@u.washington.edu.

Abstract

Emerging evidence implicates cancer stem cells (CSCs) as primary determinants of the clinical behavior of human cancers, representing an ideal target for next-generation anti-cancer therapies. However CSCs are difficult to propagate in vitro, severely limiting the study of CSC biology and drug development. Here we report that growing cells from glioblastoma (GBM) cell lines on three dimensional (3D) porous chitosan-alginate (CA) scaffolds dramatically promotes the proliferation and enrichment of cells possessing the hallmarks of CSCs. CA scaffold-grown cells were found more tumorigenic in nude mouse xenografts than cells grown from monolayers. Growing in CA scaffolds rapidly promoted expression of genes involved in the epithelial-to-mesenchymal transition that has been implicated in the genesis of CSCs. Our results indicate that CA scaffolds have utility as a simple and inexpensive means to cultivate CSCs in vitro in support of studies to understand CSC biology and develop more effective anti-cancer therapies.

Keywords: Brain tumor initiating cells; Epithelial-to-mesenchymal transition; Hyaluronic acid; Microenvironment.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alginates / chemistry
Alginates / pharmacology*
Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Cell Line, Tumor
Cell Proliferation / drug effects*
Chitosan / chemistry
Chitosan / pharmacology*
Epithelial-Mesenchymal Transition / drug effects
Glioblastoma
Glucuronic Acid / chemistry
Glucuronic Acid / pharmacology
Hexuronic Acids / chemistry
Hexuronic Acids / pharmacology
Humans
Mice
Mice, Nude
Microscopy, Electron, Scanning
Neoplastic Stem Cells / cytology
Neoplastic Stem Cells / drug effects*
Tissue Scaffolds / chemistry*
Xenograft Model Antitumor Assays

Substances

Alginates
Antineoplastic Agents
Hexuronic Acids
Glucuronic Acid
Chitosan

Abstract

Publication types

MeSH terms

Substances

Grants and funding