title: The use of nanoimprinted scaffolds as 3D culture models to facilitate spontaneous tumor cell migration and well-regulated spheroid formation.
abstract: 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.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Anagawa, Chiba 263-8555, Japan. yukiey@nirs.go.jp
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yoshii
authors.forename: Atsuo
authors.initials: A
authors.lastname: Waki
authors.forename: Kaori
authors.initials: K
authors.lastname: Yoshida
authors.forename: Anna
authors.initials: A
authors.lastname: Kakezuka
authors.forename: Maki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hideo
authors.initials: H
authors.lastname: Namiki
authors.forename: Yusei
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kiyono
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshii
authors.forename: Takako
authors.initials: T
authors.lastname: Furukawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Asai
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Okazawa
authors.forename: Juri G
authors.initials: JG
authors.lastname: Gelovani
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fujibayashi
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D051379:Mice; D018874:Spheroids, Cellular / Q000166:cytology*; D054457:Tissue Scaffolds