Review: in vitro microvessel models

Bogorad, Max I.; DeStefano, Jackson G.; Karlsson, Johan; Wong, Andrew D.; Gerecht, Sharon; Searson, Peter C.

doi:10.1039/c5lc00832h

Cited by 124 publications

(124 citation statements)

References 123 publications

(176 reference statements)

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“…The number of intravasating tumor cells has been positively correlated to the density of vessels ≥ 30 μm in diameter in tumor tissue (15), which suggests that vessels < 30 μm do not contribute significantly to intravasation. Tumor vasculature is formed quickly, typically lacking smooth muscle cells and/or pericytes, and exhibits irregular architecture often with incomplete endothelial lining (16,17); as a result, leaky tumor vessels will permit the heterogeneous extravasation of large particles and red blood cells into the perivascular space and exhibit a global permeability significantly higher than normal vasculature (12,17,18). Our vessels exhibit permeability values ranging from 10 −5 to 10 −6 cm s −1 for bovine serum albumin which is comparable to that of leaky tumor vessels (12,13).…”

Section: Resultsmentioning

confidence: 99%

“…Tumor vasculature is formed quickly, typically lacking smooth muscle cells and/or pericytes, and exhibits irregular architecture often with incomplete endothelial lining (16,17); as a result, leaky tumor vessels will permit the heterogeneous extravasation of large particles and red blood cells into the perivascular space and exhibit a global permeability significantly higher than normal vasculature (12,17,18). Our vessels exhibit permeability values ranging from 10 −5 to 10 −6 cm s −1 for bovine serum albumin which is comparable to that of leaky tumor vessels (12,13). MDA-MB-231 is a human breast adenocarcinoma cell line from triple negative breast cancer that has been shown to readily metastasize to the brain in mouse models (19,20).…”

Section: Resultsmentioning

confidence: 99%

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Mitosis-Mediated Intravasation in a Tissue-Engineered Tumor–Microvessel Platform

Wong

Searson

2017

Cancer Research

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Intravasation involves the migration of tumor cells across the local endothelium and escape into vessel flow. While tumor cell invasiveness has been correlated to increased intravasation, the details of transendothelial migration and detachment into circulation are still unclear. Here we analyzed the intravasation of invasive human breast cancer cells within a tissue-engineered microvessel model of the tumor microenvironment. Using live-cell fluorescence microscopy, we captured 2,330 hours of tumor cell interactions with functional microvessels and provide evidence for a mitosis-mediated mechanism where tumor cells located along the vessel periphery are able to disrupt the vessel endothelium through cell division and detach into circulation. This model provides a framework for understanding the physical and biological parameters of the tumor microenvironment that mediate intravasation of tumor cells across an intact endothelium.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Mitosis-Mediated Intravasation in a Tissue-Engineered Tumor–Microvessel Platform

Wong

Searson

2017

Cancer Research

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“…For example, over the course of four days, endothelial sprouts extended at ~6 μm/hr in solid fibrin gels. 11 Similarly, cocultured endothelial cells and fibroblasts required 2-3 weeks to form perfusable interconnected networks within ~1 mm 3 fibrin gels. 20 During this time, cells can only be fed through diffusion and/or interstitial flow.…”

Section: Discussionmentioning

confidence: 99%

“…3, 7, 18, 21, 35 In this approach, the scaffold is patterned by lithographic or other techniques so that it contains microfluidic channels, which are then seeded with cells. By design, this method provides precise control over vascular geometry, because the vessels form only along the original channels.…”

Section: Introductionmentioning

confidence: 99%

Physical and Chemical Signals That Promote Vascularization of Capillary-Scale Channels

et al. 2016

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Proper vascularization remains critical to the clinical application of engineered tissues. To engineer microvessels in vitro, we and others have delivered endothelial cells through preformed channels into patterned extracellular matrix-based gels. This approach has been limited by the size of endothelial cells in suspension, and results in plugging of channels below ~30 μm in diameter. Here, we examine physical and chemical signals that can augment direct seeding, with the aim of rapidly vascularizing capillary-scale channels. By studying tapered microchannels in type I collagen gels under various conditions, we establish that stiff scaffolds, forward pressure, and elevated cyclic AMP levels promote endothelial stability and that reverse pressure promotes endothelial migration. We applied these results to uniform 20-μm-diameter channels and optimized the magnitudes of pressure, flow, and shear stress to best support endothelial migration and vascular stability. This vascularization strategy is able to form millimeter-long perfusable capillaries within three days. Our results indicate how to manipulate the physical and chemical environment to promote rapid vascularization of capillary-scale channels within type I collagen gels.

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“…4a). Advances in tissue engineering provide new tools for self-organization of perfusable vascular networks that will provide the foundations for tissue engineered BBB models [67]. For example, the characteristic star-shaped morphology of human astrocytes and the low levels of activation associated with the quiescent state can be recapitulated in novel 3D matrices [68].…”

Section: Introductionmentioning

confidence: 99%

NIH workshop report on the trans-agency blood–brain interface workshop 2016: exploring key challenges and opportunities associated with the blood, brain and their interface

Ochocinska

Zloković²,

Searson³

et al. 2017

Fluids Barriers CNS

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A trans-agency workshop on the blood–brain interface (BBI), sponsored by the National Heart, Lung and Blood Institute, the National Cancer Institute and the Combat Casualty Care Research Program at the Department of Defense, was conducted in Bethesda MD on June 7–8, 2016. The workshop was structured into four sessions: (1) blood sciences; (2) exosome therapeutics; (3) next generation in vitro blood–brain barrier (BBB) models; and (4) BBB delivery and targeting. The first day of the workshop focused on the physiology of the blood and neuro-vascular unit, blood or biofluid-based molecular markers, extracellular vesicles associated with brain injury, and how these entities can be employed to better evaluate injury states and/or deliver therapeutics. The second day of the workshop focused on technical advances in in vitro models, BBB manipulations and nanoparticle-based drug carrier designs, with the goal of improving drug delivery to the central nervous system. The presentations and discussions underscored the role of the BBI in brain injury, as well as the role of the BBB as both a limiting factor and a potential conduit for drug delivery to the brain. At the conclusion of the meeting, the participants discussed challenges and opportunities confronting BBI translational researchers. In particular, the participants recommended using BBI translational research to stimulate advances in diagnostics, as well as targeted delivery approaches for detection and therapy of both brain injury and disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12987-017-0061-6) contains supplementary material, which is available to authorized users.

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Review: in vitro microvessel models

Cited by 124 publications

References 123 publications

Mitosis-Mediated Intravasation in a Tissue-Engineered Tumor–Microvessel Platform

Mitosis-Mediated Intravasation in a Tissue-Engineered Tumor–Microvessel Platform

Physical and Chemical Signals That Promote Vascularization of Capillary-Scale Channels

NIH workshop report on the trans-agency blood–brain interface workshop 2016: exploring key challenges and opportunities associated with the blood, brain and their interface

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