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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Yang, Michael T. Stapleton, Sarah C. Chen, Christopher S. Cha, Susie S. Galie, Peter A. Choi, Colin K. Nguyen, Duc-huy T. |
| Description | Author Affiliation: Nguyen DH ( Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.); |
| Abstract | Angiogenesis is a complex morphogenetic process whereby endothelial cells from existing vessels invade as multicellular sprouts to form new vessels. Here, we have engineered a unique organotypic model of angiogenic sprouting and neovessel formation that originates from preformed artificial vessels fully encapsulated within a 3D extracellular matrix. Using this model, we screened the effects of angiogenic factors and identified two distinct cocktails that promoted robust multicellular endothelial sprouting. The angiogenic sprouts in our system exhibited hallmark structural features of in vivo angiogenesis, including directed invasion of leading cells that developed filopodia-like protrusions characteristic of tip cells, following stalk cells exhibiting apical-basal polarity, and lumens and branches connecting back to the parent vessels. Ultimately, sprouts bridged between preformed channels and formed perfusable neovessels. Using this model, we investigated the effects of angiogenic inhibitors on sprouting morphogenesis. Interestingly, the ability of VEGF receptor 2 inhibition to antagonize filopodia formation in tip cells was context-dependent, suggesting a mechanism by which vessels might be able to toggle between VEGF-dependent and VEGF-independent modes of angiogenesis. Like VEGF, sphingosine-1-phosphate also seemed to exert its proangiogenic effects by stimulating directional filopodial extension, whereas matrix metalloproteinase inhibitors prevented sprout extension but had no impact on filopodial formation. Together, these results demonstrate an in vitro 3D biomimetic model that reconstitutes the morphogenetic steps of angiogenic sprouting and highlight the potential utility of the model to elucidate the molecular mechanisms that coordinate the complex series of events involved in neovascularization. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 17 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Biomimetics Microfluidics Models, Biological Morphogenesis Physiology Neovascularization, Physiologic Cell Polarity Dimethylpolysiloxanes Fingolimod Hydrochloride Fluorescent Antibody Technique Human Umbilical Vein Endothelial Cells Indoles Pharmacology Lysophospholipids Metabolism Drug Effects Propylene Glycols Pseudopodia Pyrroles Sphingosine Analogs & Derivatives Vascular Endothelial Growth Factor Receptor-2 Antagonists & Inhibitors Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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