Balance of interstitial flow magnitude and vascular endothelial growth factor concentration modulates three-dimensional microvascular network formation
Name
1.5094735.pdf
Description
Published version
Size
4.84 MB
Format
Adobe PDF
Checksum (MD5)
e00dddf1e3261305a8c84df7337b1e71
Author(s)
Abe, Yoshinori
Watanabe, Masafumi
Chung, Seok
Kamm, Roger Dale
Tanishita, Kazuo
Sudo, Ryo
Date Issued
July 2019
Journal
APL Bioengineering
Publisher
AIP Publishing
Citation
Abe, Yoshinori et al., "Balance of interstitial flow magnitude and vascular endothelial growth factor concentration modulates three-dimensional microvascular network formation." APL Bioengineering 3, 3 (September 2019): 036102 ©2019 Authors
Version
Final published version
Abstract
Hemodynamic and biochemical factors play important roles in critical steps of angiogenesis. In particular, interstitial flow has attracted attention as an important hemodynamic factor controlling the angiogenic process. Here, we applied a wide range of interstitial flow magnitudes to an in vitro three-dimensional (3D) angiogenesis model in a microfluidic device. This study aimed to investigate the effect of interstitial flow magnitude in combination with the vascular endothelial growth factor (VEGF) concentration on 3D microvascular network formation. Human umbilical vein endothelial cells (HUVECs) were cultured in a series of interstitial flow generated by 2, 8, and 25 mmH2O. Our findings indicated that interstitial flow significantly enhanced vascular sprout formation, network extension, and the development of branching networks in a magnitude-dependent manner. Furthermore, we demonstrated that the proangiogenic effect of interstitial flow application could not be substituted by the increased VEGF concentration. In addition, we found that HUVECs near vascular sprouts significantly elongated in >8 mmH2O conditions, while activation of Src was detected even in 2 mmH2O conditions. Our results suggest that the balance between the interstitial flow magnitude and the VEGF concentration plays an important role in the regulation of 3D microvascular network formation in vitro.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Department of Biological Engineering
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1063/1.5094735
