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Functional angiogenesis requires microenvironmental cues balancing endothelial cell migration and proliferation
Author(s) -
William Y. Wang,
David L. Lin,
Evan H. Jarman,
William J. Polacheck,
Brendon M. Baker
Publication year - 2020
Publication title -
lab on a chip
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.064
H-Index - 210
eISSN - 1473-0197
pISSN - 1473-0189
DOI - 10.1039/c9lc01170f
Subject(s) - angiogenesis , extracellular matrix , microbiology and biotechnology , multicellular organism , sprouting angiogenesis , endothelial stem cell , biology , cell migration , neovascularization , extracellular , cell , in vitro , cancer research , biochemistry
Angiogenesis is a complex morphogenetic process that involves intimate interactions between multicellular endothelial structures and their extracellular milieu. In vitro models of angiogenesis can aid in reducing the complexity of the in vivo microenvironment and provide mechanistic insight into how soluble and physical extracellular matrix cues regulate this process. To investigate how microenvironmental cues regulate angiogenesis and the function of resulting microvasculature, we multiplexed an established angiogenesis-on-a-chip platform that affords higher throughput investigation of 3D endothelial cell sprouting emanating from a parent vessel through defined biochemical gradients and extracellular matrix. We found that two fundamental endothelial cell functions, migration and proliferation, dictate endothelial cell invasion as single cells vs. multicellular sprouts. Microenvironmental cues that elicit excessive migration speed incommensurate with proliferation resulted in microvasculature with poor barrier function and an inability to transport fluid across the microvascular bed. Restoring the balance between migration speed and proliferation rate rescued multicellular sprout invasion, providing a new framework for the design of pro-angiogenic biomaterials that guide functional microvasculature formation for regenerative therapies.