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

被引：105

作者：

Kievit, Forrest M. ^{[1
]}

Florczyk, Stephen J. ^{[2
]}

Leung, Matthew C. ^{[2
]}

Wang, Kui ^{[2
]}

Wu, Jennifer D. ^{[3
,4
]}

Silber, John R. ^{[1
]}

Ellenbogen, Richard G. ^{[1
,5
]}

Lee, Jerry S. H. ^{[6
,7
]}

Zhang, Miqin ^{[1
,2
]}

机构：

[1] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA

[2] Univ Washington, Dept Mat Sci & Engn, Seattle, WA 98195 USA

[3] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA

[4] Med Univ S Carolina, Hollings Canc Ctr, Dept Microbiol & Immunol, Charleston, SC 29425 USA

[5] Univ Washington, Dept Radiol, Seattle, WA 98195 USA

[6] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA

[7] NCI, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA

来源：

BIOMATERIALS | 2014年 / 35卷 / 33期

基金：

美国国家卫生研究院;

关键词：

Brain tumor initiating cells; Epithelial-to-mesenchymal transition; Hyaluronic acid; Microenvironment; TUMOR-INITIATING CELLS; HYALURONAN-CD44; INTERACTIONS; BREAST-CANCER; SELF-RENEWAL; T-CELLS; GROWTH; TUMORIGENICITY; CHALLENGES; CULTURE; NOTCH;

D O I：

10.1016/j.biomaterials.2014.07.037

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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 (GEM) 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. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：9137 / 9143

页数：7

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