Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.biomaterials.2009.10.049
Title: Engineering a scaffold-free 3D tumor model for in vitro drug penetration studies
Authors: Ong, Siew-Min
Zhao, Ziqing 
Arooz, Talha
Zhao, Deqiang 
Zhang, Shufang 
Du, Tiehua
Wasser, Martin 
van Noort, Danny
Yu, Hanry 
Keywords: Science & Technology
Technology
Engineering, Biomedical
Materials Science, Biomaterials
Engineering
Materials Science
Spheroid
Liver
Synthetic inter-cellular linker
Solid tumour model
Drug penetration
EXTRACELLULAR-MATRIX
CELL-CULTURE
3-DIMENSIONAL ARCHITECTURE
SPHEROID MODEL
SOLID TUMORS
TISSUE
RESISTANCE
APOPTOSIS
CHEMOSENSITIVITY
DOXORUBICIN
Issue Date: 1-Feb-2010
Publisher: ELSEVIER SCI LTD
Citation: Ong, Siew-Min, Zhao, Ziqing, Arooz, Talha, Zhao, Deqiang, Zhang, Shufang, Du, Tiehua, Wasser, Martin, van Noort, Danny, Yu, Hanry (2010-02-01). Engineering a scaffold-free 3D tumor model for in vitro drug penetration studies. BIOMATERIALS 31 (6) : 1180-1190. ScholarBank@NUS Repository. https://doi.org/10.1016/j.biomaterials.2009.10.049
Abstract: Three-dimensional (3D) in vitro cultures are recognized for recapitulating the physiological microenvironment and exhibiting high concordance with in vivo conditions. In cancer research, the multi-cellular tumor spheroid (MCTS) model is an established 3D cancer model that exhibits microenvironmental heterogeneity close to that of tumors in vivo. However, the established process of MCTS formation is time-consuming and often uncontrolled. Here, we report a method for engineering MCTS using a transient inter-cellular linker which facilitates cell-cell interaction. Using C3A cells (a hepatocellular carcinoma cell line) as a model, we formed linker-engineered spheroids which grew to a diameter of 250 μm in 7 days, as compared to 16 days using conventional non-adherent culture. Seven-day old linker-engineered spheroids exhibited characteristics of mature MCTS, including spheroid morphology, gene expression profile, cell-cell interaction, extracellular matrix secretion, proliferation and oxygen concentration gradients, and cellular functions. Linker-engineered spheroids also displayed a resistance to drug penetration similar to mature MCTS, with dose-dependent extracellular accumulation of the drug. The linker-engineered spheroids thus provide a reliable accelerated 3D in vitro tumor model for drug penetration studies. © 2009 Elsevier Ltd. All rights reserved.
Source Title: BIOMATERIALS
URI: https://scholarbank.nus.edu.sg/handle/10635/173664
ISSN: 01429612
18785905
DOI: 10.1016/j.biomaterials.2009.10.049
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