In vitro 3D collective sprouting angiogenesis under orchestrated ANG-1 and VEGF gradients

Yoojin Shin, Jessie S. Jeon, Sewoon Han, Gi Seok Jung, Sehyun Shin, Sang Hoon Lee, Ryo Sudo, Roger D. Kamm, Seok Chung

Research output: Contribution to journalArticlepeer-review

125 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2175-2181
Number of pages7
JournalLab on a Chip
Issue number13
Publication statusPublished - 2011 Jul 7

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Chemistry(all)
  • Biomedical Engineering


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