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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

108 Scopus citations

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 invitro, 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 invitro in support of studies to understand CSC biology and develop more effective anti-cancer therapies.

Original language	English
Pages (from-to)	9137-9143
Number of pages	7
Journal	Biomaterials
Volume	35
Issue number	33
DOIs	https://doi.org/10.1016/j.biomaterials.2014.07.037
State	Published - Nov 2014
Externally published	Yes

Keywords

Brain tumor initiating cells
Epithelial-to-mesenchymal transition
Hyaluronic acid
Microenvironment

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10.1016/j.biomaterials.2014.07.037

Cite this

@article{1ee29cf3d493473db99800361725e9e8,

title = "Proliferation and enrichment of CD133+ glioblastoma cancer stem cells on 3D chitosan-alginate scaffolds",

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 invitro, 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 invitro 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",

author = "Kievit, {Forrest M.} and Florczyk, {Stephen J.} and Leung, {Matthew C.} and Kui Wang and Wu, {Jennifer D.} and Silber, {John R.} and Ellenbogen, {Richard G.} and Lee, {Jerry S.H.} and Miqin Zhang",

note = "Funding Information: This work was supported by National Institutes of Health grant R01CA172455 . FK acknowledges support from an NIH training grant ( T32CA138312 ) and an American Brain Tumor Association Fellowship in Honor of Susan Kramer. SJF acknowledges support from the Egtvedt Fellowship. We acknowledge the use of the SEM at the Dept. of Materials Science and Engineering, the confocal and optical microscopes at Keck Microscopy Imaging Facility, and the flow cytometers at the Dept. of Immunology at the University of Washington. We acknowledge laboratory assistance from Ms. Allison M. Lewis and Ms. Samara K. Sytsma in preparing CA scaffolds. We thank Prof. Benjamin S. Glick for submitting the RFP plasmid to AddGene.",

year = "2014",

month = nov,

doi = "10.1016/j.biomaterials.2014.07.037",

language = "English",

volume = "35",

pages = "9137--9143",

journal = "Biomaterials",

issn = "0142-9612",

number = "33",

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TY - JOUR

T1 - Proliferation and enrichment of CD133+ glioblastoma cancer stem cells on 3D chitosan-alginate scaffolds

AU - Kievit, Forrest M.

AU - Florczyk, Stephen J.

AU - Leung, Matthew C.

AU - Wang, Kui

AU - Wu, Jennifer D.

AU - Silber, John R.

AU - Ellenbogen, Richard G.

AU - Lee, Jerry S.H.

AU - Zhang, Miqin

N1 - Funding Information: This work was supported by National Institutes of Health grant R01CA172455 . FK acknowledges support from an NIH training grant ( T32CA138312 ) and an American Brain Tumor Association Fellowship in Honor of Susan Kramer. SJF acknowledges support from the Egtvedt Fellowship. We acknowledge the use of the SEM at the Dept. of Materials Science and Engineering, the confocal and optical microscopes at Keck Microscopy Imaging Facility, and the flow cytometers at the Dept. of Immunology at the University of Washington. We acknowledge laboratory assistance from Ms. Allison M. Lewis and Ms. Samara K. Sytsma in preparing CA scaffolds. We thank Prof. Benjamin S. Glick for submitting the RFP plasmid to AddGene.

PY - 2014/11

Y1 - 2014/11

N2 - 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 invitro, 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 invitro in support of studies to understand CSC biology and develop more effective anti-cancer therapies.

AB - 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 invitro, 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 invitro in support of studies to understand CSC biology and develop more effective anti-cancer therapies.

KW - Brain tumor initiating cells

KW - Epithelial-to-mesenchymal transition

KW - Hyaluronic acid

KW - Microenvironment

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