In vitro 3D collective sprouting angiogenesis under orchestrated ANG-1 and VEGF gradients (original) (raw)
* Corresponding authors
a School of Mechanical Engineering, Korea University, 512B, Changui Bldg, 5-1, Anam, Seongbuk, Seoul, Korea
E-mail: sidchung@korea.ac.kr
Tel: +82 2 3290 3352
b Department of Biomedical Engineering, Korea University, Seoul, Korea
c Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
d Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
e Department of System Design Engineering, Keio University, Yokohama, Japan
Abstract
Sprouting angiogenesis requires a coordinated guidance from a variety of angiogenic factors. Here, we have developed a unique hydrogel incorporating microfluidic platform which mimics the physiological microenvironment in 3D under a precisely orchestrated gradient of soluble angiogenic factors, VEGF and ANG-1. The system enables the quantified investigation in chemotactic response of endothelial cells during the collective angiogenic sprouting process. While the presence of a VEGF gradient alone was sufficient in inducing a greater number of tip cells, addition of ANG-1 to the VEGF gradient enhanced the number of tip cells that are attached to collectively migrated stalk cells. The chemotactic response of tip cells attracted by the VEGF gradient and the stabilizing role of ANG-1 were morphologically investigated, elucidating the 3D co-operative migration of tip and stalk cells as well as their structures. We found that ANG-1 enhanced the connection of the stalk cells with the tip cells, and then the direct connection regulated the morphogenesis and/or life cycle of stalk cells.
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Article information
DOI
https://doi.org/10.1039/C1LC20039A
Article type
Paper
Submitted
14 Jan 2011
Accepted
18 Apr 2011
First published
26 May 2011
Download Citation
Lab Chip, 2011,11, 2175-2181
Permissions
In vitro 3D collective sprouting angiogenesis under orchestrated ANG-1 and VEGF gradients
Y. Shin, J. S. Jeon, S. Han, G. Jung, S. Shin, S. Lee, R. Sudo, R. D. Kamm and S. Chung,Lab Chip, 2011, 11, 2175DOI: 10.1039/C1LC20039A
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