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
Joris Pauty,
Ryo Usuba,
Irene Gayi Cheng,
Louise Hespel,
Haruko Takahashi,
Keisuke Kato,
Masayoshi Kobayashi,
Hiroyuki Nakajima,
Eujin Lee,
Florian Yger,
Fabrice Soncin,
Yukiko T. Matsunaga
Affiliations
Joris Pauty
Center for International Research on Integrative Biomedical Systems (CIBiS), Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
Ryo Usuba
Center for International Research on Integrative Biomedical Systems (CIBiS), Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
Irene Gayi Cheng
Department of Bioengineering, Clemson University, 118 Engineering Service Dr., Clemson, SC 29634, USA
Louise Hespel
Ecole Normale Supérieure-PSL Research University, Département de Chimie, Sorbonne Universités, UPMC Université Paris 06, CNRS UMR 8640 PASTEUR, 24 rue Lhomond, 75005 Paris, France
Haruko Takahashi
Center for International Research on Integrative Biomedical Systems (CIBiS), Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
Keisuke Kato
R&D Department 1, SCREEN Holdings Co., Ltd., 322 Furukawa-cho, Hazukashi, Fushimi-ku, Kyoto 612-8486, Japan
Masayoshi Kobayashi
R&D Department 1, SCREEN Holdings Co., Ltd., 322 Furukawa-cho, Hazukashi, Fushimi-ku, Kyoto 612-8486, Japan
Hiroyuki Nakajima
Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan
Eujin Lee
Center for International Research on Integrative Biomedical Systems (CIBiS), Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
Florian Yger
LAMSADE, CNRS UMR 7243, Université Paris-Dauphine, PSL Research University, 75016 Paris, France
Fabrice Soncin
CNRS/IIS/COL/Université Lille 1 SMMiL-E project, CNRS Délégation Nord-Pas de Calais et Picardie, 2 rue de Canonniers, Lille, Cedex 59046, France
Yukiko T. Matsunaga
Center for International Research on Integrative Biomedical Systems (CIBiS), Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
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.
