Document Detail

Engineering a scaffold-free 3D tumor model for in vitro drug penetration studies.
MedLine Citation:
PMID:  19889455     Owner:  NLM     Status:  MEDLINE    
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 microm 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.
Siew-Min Ong; Ziqing Zhao; Talha Arooz; Deqiang Zhao; Shufang Zhang; Tiehua Du; Martin Wasser; Danny van Noort; Hanry Yu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-03
Journal Detail:
Title:  Biomaterials     Volume:  31     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-29     Completed Date:  2010-03-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  1180-90     Citation Subset:  IM    
Copyright Information:
(c) 2009 Elsevier Ltd. All rights reserved.
Institute of Bioengineering and Nanotechnology, Agency for Science, Technology and Research (A* STAR), The Nanos, 31 Biopolis Way, Singapore 138669, Singapore.
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MeSH Terms
Biological Assay / methods*
Carcinoma, Hepatocellular / drug therapy,  metabolism*,  pathology
Cell Culture Techniques / methods
Cell Line, Tumor
Doxorubicin / administration & dosage,  pharmacokinetics*
Drug Evaluation, Preclinical / methods*
Spheroids, Cellular / drug effects,  metabolism*
Tissue Engineering / methods*
Reg. No./Substance:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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