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A Vascular Endothelial Growth Factor-Dependent Sprouting Angiogenesis Assay Based on an In Vitro Human Blood Vessel Model for the Study of Anti-Angiogenic Drugs

Pauty, Joris; Usuba, Ryo; Cheng, Irene Gayi; Hespel, Louise; Takahashi, Haruko; Kato, Keisuke; Kobayashi, Masayoshi; Nakajima, Hiroyuki; Lee, Eujin; Yger, Florian; Soncin, Fabrice; Matsunaga, Yukiko (2018), A Vascular Endothelial Growth Factor-Dependent Sprouting Angiogenesis Assay Based on an In Vitro Human Blood Vessel Model for the Study of Anti-Angiogenic Drugs, EBioMedicine, 27, p. 225-236. 10.1016/j.ebiom.2017.12.014

Type
Article accepté pour publication ou publié
Date
2018
Journal name
EBioMedicine
Volume
27
Pages
225-236
Publication identifier
Metadata
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Author(s)
Pauty, Joris
University of Tokyo
Usuba, Ryo
University of Tokyo
Cheng, Irene Gayi
autre
Hespel, Louise cc
Ecole Normale Supérieure - Département de Chimie
Takahashi, Haruko
University of Tokyo
Kato, Keisuke
autre
Kobayashi, Masayoshi
autre
Nakajima, Hiroyuki
autre
Lee, Eujin
University of Tokyo
Yger, Florian cc
Laboratoire d'analyse et modélisation de systèmes pour l'aide à la décision [LAMSADE]
Soncin, Fabrice
Institut de biologie de Lille - UMS 3702 [IBL]
Matsunaga, Yukiko
University of Tokyo
Abstract (EN)
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.
Subjects / Keywords
Angiogenesis inhibitors; DLL4; Human umbilical vein endothelial cell; In vitro 3D model; Microvessel; Notch; Sorafenib; Sprouting angiogenesis; Sunitinib; Vascular endothelial growth factor