期刊
EBIOMEDICINE
卷 27, 期 -, 页码 225-236出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2017.12.014
关键词
Angiogenesis inhibitors; DLL4; Human umbilical vein endothelial cell; In vitro 3D model; Microvessel; Notch; Sorafenib; Sprouting angiogenesis; Sunitinib; Vascular endothelial growth factor
资金
- Japan Society for the Promotion of Science (JSPS)
- Foundation for the Promotion of Industrial Science (FPIS)
- Ligue Regionale contre le cancer
- SFR Cancer Lille
- Grants-in-Aid for Scientific Research [16H06686, 15F15767] Funding Source: KAKEN
Angiogenesis is the formation of new capillaries from pre-existing blood vessels and participates in proper vasculature development. In pathological conditions such as cancer, abnormal angiogenesis takes place. Angiogenesis is primarily carried out by endothelial cells, the innermost layer of blood vessels. The vascular endothelial growth factor-A (VEGF-A) and its receptor-2 (VEGFR-2) trigger most of the mechanisms activating and regulating angiogenesis, and have been the targets for the development of drugs. However, most experimental assays assessing angiogenesis rely on animal models. We report an in vitro model using a microvessel-on-a-chip. It mimics an effective endothelial sprouting angiogenesis event triggered from an initial microvessel using a single angiogenic factor, VEGF-A. The angiogenic sprouting in this model is depends on the Notch signaling, as observed in vivo. This model enables the study of anti-angiogenic drugs which target a specific factor/receptor pathway, as demonstrated by the use of the clinically approved sorafenib and sunitinib for targeting the VEGF-A/VEGFR-2 pathway. Furthermore, this model allows testing simultaneously angiogenesis and permeability. It demonstrates that sorafenib impairs the endothelial barrier function, while sunitinib does not. Such in vitro human model provides a significant complimentary approach to animal models for the development of effective therapies. (c) 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.
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