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: 225-236, 2018 Jan.
Article
em En
| MEDLINE
| ID: mdl-29289530
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Bioensaio
/
Vasos Sanguíneos
/
Neovascularização Fisiológica
/
Inibidores da Angiogênese
/
Fator A de Crescimento do Endotélio Vascular
/
Modelos Biológicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
EBioMedicine
Ano de publicação:
2018
Tipo de documento:
Article