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Microfluidic Platforms for Studies of Angiogenesis, Cell Migration, and Cell–Cell Interactions

Sixth International Bio-Fluid Mechanics Symposium and Workshop March 28–30, 2008 Pasadena, California

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Abstract

Recent advances in microfluidic technologies have opened the door for creating more realistic in vitro cell culture methods that replicate many aspects of the true in vivo microenvironment. These new designs (i) provide enormous flexibility in controlling the critical biochemical and biomechanical factors that influence cell behavior, (ii) allow for the introduction of multiple cell types in a single system, (iii) provide for the establishment of biochemical gradients in two- or three-dimensional geometries, and (iv) allow for high quality, time-lapse imaging. Here, some of the recent developments are reviewed, with a focus on studies from our own laboratory in three separate areas: angiogenesis, cell migration in the context of tumor cell-endothelial interactions, and liver tissue engineering.

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Notes

  1. Different from 2D migration, steps of 3D cell migration can be arranged in five steps; Pseudopod protrusion at the leading edge, formation of focal contact, focalized proteolysis, actomyosin contraction, and detachment of tailing edge.28 Cells on 2D flat substrate cannot have epithelial cell polarity, and also often have different patterns of gene expression. Growth, motility, differentiation, and morphogenesis are different due to 3D matrix-dependent regulation in 3D environments.92 For example, epithelial cells form 3D lumen structures with epithelial polarity and mesenchymal cells lie in the ECM. Two-dimensional migration models cannot represent the whole 3D structures and also 3D matrix-induced morphogenesis such as vessel sprouting and branching. Three-dimensional migration of tumor cell also has diversity of amoeboid migration, mesenchymal single cell or chain migration and other collective movements forming cluster or multicellular strands or sheets.28 Considering tissue engineering applications used to restore, maintain, or enhance tissues and organs, we need a better understanding of 3D structures and responses of cells.2,3,34,35,53,59 To engineer living tissues in vitro, cultured cell are coaxed to grow on bioactive degradable scaffolds that provide the physical and chemical cues to guide their differentiation and assembly into 3D tissues.35

Abbreviations

2D:

Two-dimensional

3D:

Three-dimensional

ECIS:

Electric cell-substrate impedance sensing

ECM:

Extracellular matrix

EC:

Endothelial cell

SEC:

Sinusoidal endothelial cell

EGF:

Epidermal growth factor

hMVEC:

Human microvascular endothelial cells

HSC:

Hepatic stellate cell

PDMS:

Polydimethylsiloxane

VEGF:

Vascular endothelial growth factor

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Acknowledgments

The authors would like to express their gratitude to Draper Laboratories (IR&D Project N. DL-H-550151), the National Science Foundation (EFRI-0735997), the NHLBI (EB003805), and the Singapore-MIT Alliance for Research and Technology.

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Authors and Affiliations

  1. School of Mechanical Engineering, Korea University, Seoul, Korea

    Seok Chung

  2. Department of System Design Engineering, Keio University, Yokohama, Japan

    Ryo Sudo

  3. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Vernella Vickerman

  4. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Ioannis K. Zervantonakis & Roger D. Kamm

  5. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Roger D. Kamm

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  1. Seok Chung
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  2. Ryo Sudo
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  3. Vernella Vickerman
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  4. Ioannis K. Zervantonakis
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  5. Roger D. Kamm
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Corresponding author

Correspondence to Roger D. Kamm.

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Associate Editor Larry V. McIntire oversaw the review of this article.

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Chung, S., Sudo, R., Vickerman, V. et al. Microfluidic Platforms for Studies of Angiogenesis, Cell Migration, and Cell–Cell Interactions. Ann Biomed Eng 38, 1164–1177 (2010). https://doi.org/10.1007/s10439-010-9899-3

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  • DOI: https://doi.org/10.1007/s10439-010-9899-3

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