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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

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Date
2018
Dewey
Maladies
Sujet
Angiogenesis inhibitors; DLL4; Human umbilical vein endothelial cell; In vitro 3D model; Microvessel; Notch; Sorafenib; Sprouting angiogenesis; Sunitinib; Vascular endothelial growth factor
Journal issue
EBioMedicine
Volume
27
Publication date
01-2018
Article pages
225-236
DOI
http://dx.doi.org/10.1016/j.ebiom.2017.12.014
URI
https://basepub.dauphine.fr/handle/123456789/17483
Collections
  • LAMSADE : Publications
Metadata
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Author
Pauty, Joris
21538 University of Tokyo
Usuba, Ryo
21538 University of Tokyo
Cheng, Irene Gayi
115536 autre
Hespel, Louise
74000 Ecole Normale Supérieure - Département de Chimie
Takahashi, Haruko
21538 University of Tokyo
Kato, Keisuke
115536 autre
Kobayashi, Masayoshi
115536 autre
Nakajima, Hiroyuki
115536 autre
Lee, Eujin
21538 University of Tokyo
Yger, Florian
989 Laboratoire d'analyse et modélisation de systèmes pour l'aide à la décision [LAMSADE]
Soncin, Fabrice
44867 Institut de biologie de Lille - UMS 3702 [IBL]
Matsunaga, Yukiko
21538 University of Tokyo
Type
Article accepté pour publication ou publié
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.

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