萌芽血管生成
血管生成
发芽
细胞生物学
表型
生物
间质细胞
调节器
新生血管
神经科学
化学
癌症研究
遗传学
基因
植物
作者
Sudong Kim,Minhwa Chung,Jung Yong Ahn,Somin Lee,Noo Li Jeon
出处
期刊:Lab on a Chip
[The Royal Society of Chemistry]
日期:2016-01-01
卷期号:16 (21): 4189-4199
被引量:170
摘要
A crucial yet ill-defined phenomenon involved in the remodeling of vascular networks, including angiogenic sprouting, is flow-mediated endothelial dynamics and phenotype changes. Despite interstitial flow (IF) being ubiquitously present in living tissues surrounding blood capillaries, it is rarely investigated and poorly understood how endothelial cells respond to this flow during morphogenesis. Here we develop a microfluidic 3D in vitro model to investigate the role of IF during vasculogenic formation and angiogenic remodeling of microvascular networks. In the presented model, human blood endothelial cells co-cultured with stromal fibroblasts spontaneously organize into an interconnected microvascular network and then further expand to adjacent avascular regions in a manner of neovessel sprouting. We found that in the presence of IF, vasculogenic organization of the microvascular network was significantly facilitated regardless of the flow direction, whereas angiogenic sprouting was promoted only when the directions of flow and sprouting were opposite while angiogenic activity was suppressed into the direction of flow. We also observed that the vasculatures switch between active angiogenic remodeling and quiescent/non-sprouting state in the contexts provided by IF. This regulatory effect can be utilized to examine the role of anti-angiogenic compounds, clearly distinguishing the differential influences of the compounds depending on their mechanisms of action. Collectively, these results suggest that IF may serve as a critical regulator in tissue vascularization and pathological angiogenesis.
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