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発表内容

Title:
Cellular Building Blocks for 3D Tissue Construction

Shoji Takeuchi, Associate Professor
Center for International Research on Micronano Mechatronics(CIRMM),
The University of Tokyo

Abstract:
In this presentation, I will talk about several MEMS/Microfluidic-based approaches for the rapid construction of large-scale 3D tissue that mimic microscopic tissue structures in vivo . We demonstrated a bottom-up tissue construction method using different types of cellular modules that serve as building blocks for thick and dense 3D tissues (eg. cell beads and cell fibers).
To prepare the cellular beads, we used an axisymmetric flow focusing device (AFFD) that allows us to encapsulate cells within monodisperse collagen beads. By putting these cellular microcapsules in a 3D chamber and incubating them, we built a complicated and milli-sized 3D structure (Advanced Materials, vol. 23, pp. H90-94, 2011).
As the fiber-shaped cellular building units, a cell- encapsulating core-shell hydrogel fiber was produced in a double coaxial laminar flow microfluidic device (Nature Materials, vol.2, pp. 584?590, 2013). The cells cultured in the fiber show excellent intrinsic functions. When with myocytes, endothelial, and nerve cells, they showed the contractile motion of the myocyte cell fiber, the tube formation of the endothelial cell fibers and the synaptic connections of the nerve cell fiber, respectively.
By using microfluidic handling, higher-order assembly of fiber-shaped 3D cellular constructs can be performed. In particular, mechanical weaving of cell fibers with our lab-made microfluidic weaving machine provides a woven “cell fabric” composed of three different cell fibers within 3 h in a culture medium. As the practical application, the fiber encapsulating beta-cells is used for the implantation of diabetic mice, and succeeded in normalizing the blood glucose level.

References:
1. Hiroaki Onoe, Teru Okitsu, Akane Itou, Midori Kato-Negishi, Riho Gojo, Daisuke Kiriya, Koji Sato, Shigenori Mirua, Shintaroh Iwanaga, Kaori Kuribayashi-Shigetomi, Yukiko Matsunaga, Yuto Shimoyama, and Shoji Takeuchi: Metre-long Cellular Microfibres Exhibiting Tissue Morphologies and Functions, Nature Materials , vol.12, pp. 584?590, 2013

2 . Kaori Kuribayashi-Shigetomi, Hiroaki Onoe, and Shoji Takeuchi: Cell Origami: Self-folding of Three-Dimensional Cell-Laden Microstructures Driven by Cell Traction Force, PLoS ONE , vol. 7(12), p. e51085, 2012

3. Yukiko T Matsunaga*, Yuya Morimoto*, and Shoji Takeuchi: Molding cell beads for rapid construction of macroscopic 3D tissue architecture, Advanced Materials , vol. 23, pp. H90-94, 2011

4. N. Misawa, H. Mitsuno, R. Kanzaki, S. Takeuchi: A Highly Sensitive and Selective Odorant Sensor using Living Cells Expressing Insect Olfactory Receptors, Proc. Natl. Acad. Sci. USA , vol. 107(35), pp. 15340-15344, 2010

5. W-H. Tan and Shoji Takeuchi: A Trap-and-Release Integrated Microfluidic System for Dynamic Microarray Applications, Proc. Natl. Acad. Sci. USA , vol. 104, no. 4, pp. 1146-1151, 2007