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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2019.01011

Imaging the Dynamic Interaction Between Sprouting Microvessels and the Extracellular Matrix

 Adam Rauff1, 2, Steven A. LaBelle1, 2, Hannah A. Strobel3, James B. Hoying3 and  Jeffrey Weiss1, 2*
  • 1Department of Biomedical Engineering, College of Engineering, University of Utah, United States
  • 2Scientific Computing and Imaging Institute, University of Utah, United States
  • 3Advanced Solutions Life Science (ASLS), United States

Thorough understanding of growth and evolution of tissue vasculature is fundamental to many fields of medicine including cancer therapy, wound healing, and tissue engineering. Angiogenesis, the growth of new vessels from existing ones, is dynamically influenced by a variety of environmental factors, including mechanical and biophysical factors, chemotactic factors, proteolysis, and interaction with stromal cells. Yet, dynamic interactions between neovessels and their environment are difficult to study with traditional fixed time imaging techniques. Advancements in imaging technologies permit time-series and volumetric imaging, affording the ability to visualize microvessel growth over 3D space and time. Time-lapse imaging has led to more informative investigations of angiogenesis. The environmental factors implicated in angiogenesis span a wide range of signals. Neovessels advance through stromal matrices by forming attachments and pulling and pushing on their microenvironment, reorganizing matrix fibers, and inducing large deformations of the surrounding stroma. Concurrently, neovessels secrete proteolytic enzymes to degrade their basement membrane, create space for new vessels to grow, and release matrix-bound cytokines. Growing neovessels also respond to a host of soluble and matrix-bound growth factors, and display preferential growth along a cytokine gradient. Lastly, stromal cells such as macrophages and mesenchymal stem cells interact directly with neovessels and their surrounding matrix to facilitate sprouting, vessel fusion, and tissue remodeling. This review highlights how time-lapse imaging techniques advanced our understanding of the interaction of blood vessels with their environment during sprouting angiogenesis. The technology provides means to characterize the evolution of microvessel behavior, providing new insights and holding great promise for further research on the process of angiogenesis.

Keywords: Angiogenesis, Neovessels, vascular networks, time-series imaging, Extracellular Matrix

Received: 20 Feb 2019; Accepted: 22 Jul 2019.

Copyright: © 2019 Rauff, LaBelle, Strobel, Hoying and Weiss. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Jeffrey Weiss, Department of Biomedical Engineering, College of Engineering, University of Utah, Salt Lake City, 84112-9458, Utah, United States,