期刊
BIOMATERIALS
卷 34, 期 38, 页码 10143-10150出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.09.034
关键词
Spheroid; Cancer stem cell; Multidrug resistance; Invasion; Glioma
资金
- Washington Research Foundation
- Kyocera Professorship Endowment
- Egtvedt Fellowship
- NIH [T32CA138312]
- College of Engineering Dean's Fellowship at University of Washington
Cancer therapeutics are developed through extensive screening; however, many therapeutics evaluated with 2D in vitro cultures during pre-clinical trials suffer from lower efficacy in patients. Replicating the in vivo tumor microenvironment in vitro with three-dimensional (3D) porous scaffolds offers the possibility of generating more predictive pre-clinical models to enhance cancer treatment efficacy. We developed a chitosan and hyaluronic acid (HA) polyelectrolyte complex 3D porous scaffold and evaluated its physical properties. Chitosan-HA (C-HA) scaffolds had a highly porous network. C-HA scaffolds were compared to 2D surfaces for in vitro culture of U-118 MG human glioblastoma (GBM) cells. C-HA scaffold cultures promoted tumor spheroid formation and increased stem-like properties of GBM cells as evidenced by the upregulation of CD44, Nestin, Musashi-1, GFAP, and HIF-1 alpha as compared with 2D cultures. Additionally, the invasiveness of GBM cells cultured in C-HA scaffolds was significantly enhanced compared to those grown in 2D cultures. C-HA scaffold cultures were also more resistant to chemotherapy drugs, which corresponded to the increased expression of ABCG2 drug efflux transporter. These findings suggest that C-HA scaffolds offer promise as an in vitro GBM platform for study and screening of novel cancer therapeutics. (C) 2013 Elsevier Ltd. All rights reserved.
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