Evidence map›Paper›PMID 28608153›Full record

ArticleAngiogenesis2017

Low levels of physiological interstitial flow eliminate morphogen gradients and guide angiogenesis.

Venktesh S Shirure, Andrew Lezia, Arnold Tao, Luis F Alonzo, Steven C George

Open access · greenAbstract read
In one paragraph

Article in Angiogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

75 citing papers in PubMed, 115 citations in OpenAlex.

  1. Review
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  9. Bridging the Gap Between Static Histology and Dynamic Organ-on-a-Chip Models.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Review
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15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Venktesh S ShirureDepartment of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, 63130, USA.
Andrew LeziaDepartment of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, 63130, USA.
Arnold TaoDepartment of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, 63130, USA.
Luis F AlonzoDepartment of Biomedical Engineering, University of California, Irvine, CA, 92697, USA.
Steven C GeorgeDepartment of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, 63130, USA. scg@wustl.edu.
Washington University in St. Louis · USUniversity of California, Irvine · US

Funding

Linking DDR2 expression, the cancer-associated fibroblast, and angiogenesis in the tumor microenvironmentUH3TR000481 · NCATS · WASHINGTON UNIVERSITY · PI GEORGE, STEVEN CARL · 2014 to 2016
$2.8M
A 3-D In Vitro Platform of Tumor Metastasis (PQ24)R01CA170879 · NCI · WASHINGTON UNIVERSITY · PI GEORGE, STEVEN CARL · 2012 to 2015
$1.3M
Center for Clinical and Translational ScienceKL2TR000048 · NCATS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI AZAR, DIMITRI T, MERMELSTEIN, ROBIN J. · 2012 to 2014
$559k
Creating a 3D dynamic in vitro model of the tumor microenvironment to characterizF31CA163049 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI ALONZO, LUIS FERNANDO · 2011 to 2013
$107k
NCATS NIH HHS KL2 TR000048NCATS NIH HHS UH3 TR000481NCI NIH HHS F31 CA163049NCI NIH HHS R01 CA170879
6 · The paper itself

Abstract

Convective transport can significantly distort spatial concentration gradients. Interstitial flow is ubiquitous throughout living tissue, but our understanding of how interstitial flow affects concentration gradients in biological processes is limited. Interstitial flow is of particular interest for angiogenesis because pathological and physiological angiogenesis is associated with altered interstitial flow, and both interstitial flow and morphogen gradients (e.g., vascular endothelial growth factor, VEGF) can potentially stimulate and guide new blood vessel growth. We designed an in vitro microfluidic platform to simulate 3D angiogenesis in a tissue microenvironment that precisely controls interstitial flow and spatial morphogen gradients. The microvascular tissue was developed from endothelial colony forming cell-derived endothelial cells extracted from cord blood and stromal fibroblasts in a fibrin extracellular matrix. Pressure in the microfluidic lines was manipulated to control the interstitial flow. A mathematical model of mass and momentum transport, and experimental studies with fluorescently labeled dextran were performed to validate the platform. Our data demonstrate that at physiological interstitial flow (0.1-10 μm/s), morphogen gradients were eliminated within hours, and angiogenesis demonstrated a striking bias in the opposite direction of interstitial flow. The interstitial flow-directed angiogenesis was dependent on the presence of VEGF, and the effect was mediated by αvβ3 integrin. We conclude that under physiological conditions, growth factors such as VEGF and fluid forces work together to initiate and spatially guide angiogenesis.

Indexed as

Neovascularization, PhysiologicDiffusionExtracellular FluidHumansIntegrin alphaVbeta3MicrofluidicsVascular Endothelial Growth Factor AIntegrin alphaVbeta3Vascular Endothelial Growth Factor AConcentration gradientsMicrophysiological systemsOrgan-on-a-chipαvβ3 integrin

Identifiers

PMID28608153
PMCPMC10597324
OpenAlexW2626955070

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.