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Biomaterials. 2011 Sep;32(26):6052-8. doi: 10.1016/j.biomaterials.2011.04.076. Epub 2011 Jun 2.

The use of nanoimprinted scaffolds as 3D culture models to facilitate spontaneous tumor cell migration and well-regulated spheroid formation.

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Molecular Imaging Center, National Institute of Radiological Sciences, Anagawa, Chiba 263-8555, Japan.


Two-dimensional (2D) cell cultures are essential for drug development and tumor research. However, the limitations of 2D cultures are widely recognized, and a better technique is needed. Recent studies have indicated that a strong physical contact between cells and 2D substrates induces cellular characteristics that differ from those of tumors growing in vivo. 3D cell cultures using various substrates are then developing; nevertheless, conventional approaches have failed in maintenance of cellular proliferation and viability, uniformity, reproducibility, and/or simplicity of these assays. Here, we developed a 3D culture system with inorganic nanoscale scaffolding using nanoimprinting technology (nano-culture plates), which reproduced the characteristics of tumor cells growing in vivo. Diminished cell-to-substrate physical contact facilitated spontaneous tumor cell migration, intercellular adhesion, and multi-cellular 3D-spheroid formation while maintaining cellular proliferation and viability. The resulting multi-cellular spheroids formed hypoxic core regions similar to tumors growing in vivo. This technology allows creating uniform and highly-reproducible 3D cultures, which is easily applicable for microscopic and spectrophotometric assays, which can be used for high-throughput/high-content screening of anticancer drugs and should accelerate discovery of more effective anticancer therapies.

[Indexed for MEDLINE]

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