[Frontiers in Bioscience E5, 37-48, January 1, 2013]

Microtechnology-based three-dimensional spheroid formation

Hiroki Ota1, Norihisa Miki1

1Department of Mechanical Engineering, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522 Japan


1. Abstract
2. Introduction
3. MicroRNA biogenesis and functions
4. MicroRNA expression profiles in liver cancer
5. Oncogenic miRNAs in human HCC
6. Tumor suppressive miRNA in human HCC
7. miRNA sequence variants in HCC
8. Diagnosis and prognosis values of miRNA
9. Therapeutic potentials of miRNA
10. Summary and perspectives
11. Acknowledgements
12. References


This article highlights the current state of three-dimensional spheroid/tissue formation technologies offering a new experimental platform that is both as reproducible as conventional in vitro experiments and highly correlated to in vivo conditions. Three-dimensional tissue exhibit higher biological functions and reflect the in vivo context more precisely than classical two-dimensional cultures or monolayers. The applications cover highly efficient drug screening, regenerative medicine and fundamental biological research. Numerous three-dimensional spheroid and tissue formation devices have been developed over the past six decades. In early studies, mass production of spheroids using shaking, and non-adhesive surfaces and scaffolds in flasks was conducted. With the emergence of micro/nano fabrication technology and fundamental understanding of micro/nano fluidics, micro/nano devices capable of forming three-dimensional spheroids in a well-controlled manner have been extensively studied. The cell species composing spheroids include hepatic cells, cancer cells, primary cells and, more recently, stem cells. Formation of hetero-spheroids composed of different cells has also been attempted to further resemble the in vivo conditions. These new trends in spheroid research are particularly highlighted in this review.