Evidence map›Paper›PMID 24090675›Full record

ArticleJournal of molecular and cellular cardiology2013

SLIT3-ROBO4 activation promotes vascular network formation in human engineered tissue and angiogenesis in vivo.

Jonathan D Paul, Kareen L K Coulombe, Peter T Toth, Yanmin Zhang, Glenn Marsboom, Vytas P Bindokas, David W Smith, Charles E Murry, Jalees Rehman

Open access · hybridAbstract read
In one paragraph

Article in Journal of molecular and cellular cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 11% 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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
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  12. Article
  13. SLIT3-mediated fibroblast signaling: a promising target for antifibrotic therapies.American journal of physiology. Heart and circulatory physiology · 2023
    Review
  14. Article
  15. Article
  16. Article
  17. Type H vessels: functions in bone development and diseases.Frontiers in cell and developmental biology · 2023
    Review
  18. Article
  19. Effect of Angiogenesis in Bone Tissue Engineering.Annals of biomedical engineering · 2022
    Review
  20. Review
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

9 authors at 3 institutions in 1 country.

Jonathan D Paul *Section of Cardiology, Department of Medicine, University of Chicago, Chicago, IL.
Kareen L K Coulombe *Department of Pathology, Center for Cardiovascular Biology, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA.
Peter T TothResearch Resources Center, University of Illinois at Chicago, Chicago, IL.
Yanmin ZhangDepartment of Pharmacology, University of Illinois at Chicago, Chicago, IL.
Glenn MarsboomDepartment of Pharmacology, University of Illinois at Chicago, Chicago, IL.
Vytas P BindokasIntegrated Microscopy Core Facility, University of Chicago, Chicago, IL.
David W SmithDepartment of Pathology, Center for Cardiovascular Biology, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA.
Charles E MurryDepartment of Pathology, Center for Cardiovascular Biology, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA.
Jalees RehmanDepartment of Pharmacology, University of Illinois at Chicago, Chicago, IL.
University of Illinois Chicago · USUniversity of Washington · USUniversity of Chicago · US

Funding

Self Renewal and Differentiation of Human Embryonic Stem CellsP01GM081619 · NIGMS · UNIVERSITY OF WASHINGTON · PI RUOHOLA-BAKER, HANNELE · 2007 to 2017
$20.6M
Vascularization and Growth of Human Myocardial GraftsP01HL094374 · NHLBI · UNIVERSITY OF WASHINGTON · PI MINAMI, ELINA · 2010 to 2014
$14.5M
MULTIDISCIPLINARY CARDIAC SCIENCEST32HL007381 · NHLBI · UNIVERSITY OF CHICAGO · PI JEANNE M DECARA, Yoav Gilad · 1985 to 2026
$12.5M
EXPERIMENTAL PATHOLOGY OF CARDIOVASCULAR DISEASET32HL007312 · NHLBI · UNIVERSITY OF WASHINGTON · PI MAJESKY, MARK W., SCHWARTZ, STEPHEN MARK · 1985 to 2019
$11.8M
Expansion of cardiac and hematopoietic progenitors by Wnt and NotchU01HL100405 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, JONATHAN A., MORRISEY, EDWARD E · 2009 to 2015
$8.1M
Cell-Based Cardiac RepairR01HL084642 · NHLBI · UNIVERSITY OF WASHINGTON · PI MURRY, CHARLES E · 2007 to 2014
$4.9M
The role of mitochondria in embryonic stem cells.R01GM094220 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI REHMAN, JALEES · 2011 to 2015
$1.5M
The Effects of Reactive Oxygen Species on Endothelial Progenitor CellsK08HL080082 · NHLBI · UNIVERSITY OF CHICAGO · PI REHMAN, JALEES · 2006 to 2010
$665k
NHLBI NIH HHS K08 HL080082NHLBI NIH HHS K08-HL080082NHLBI NIH HHS P01 HL094374NHLBI NIH HHS P01-HL094374NHLBI NIH HHS R01 HL084642NHLBI NIH HHS R01-HL084642NHLBI NIH HHS T32 HL007312NHLBI NIH HHS T32-HL007312NHLBI NIH HHS T32 HL007381NHLBI NIH HHS T32-HL007381NHLBI NIH HHS U01 HL100405NHLBI NIH HHS U01-HL100405NIGMS NIH HHS P01 GM081619NIGMS NIH HHS P01-GM81619NIGMS NIH HHS R01 GM094220NIGMS NIH HHS R01-GM094220
6 · The paper itself

Abstract

Successful implantation and long-term survival of engineered tissue grafts hinges on adequate vascularization of the implant. Endothelial cells are essential for patterning vascular structures, but they require supportive mural cells such as pericytes/mesenchymal stem cells (MSCs) to generate stable, functional blood vessels. While there is evidence that the angiogenic effect of MSCs is mediated via the secretion of paracrine signals, the identity of these signals is unknown. By utilizing two functionally distinct human MSC clones, we found that so-called "pericytic" MSCs secrete the pro-angiogenic vascular guidance molecule SLIT3, which guides vascular development by directing ROBO4-positive endothelial cells to form networks in engineered tissue. In contrast, "non-pericytic" MSCs exhibit reduced activation of the SLIT3/ROBO4 pathway and do not support vascular networks. Using live cell imaging of organizing 3D vascular networks, we show that siRNA knockdown of SLIT3 in MSCs leads to disorganized clustering of ECs. Knockdown of its receptor ROBO4 in ECs abolishes the generation of functional human blood vessels in an in vivo xenogenic implant. These data suggest that the SLIT3/ROBO4 pathway is required for MSC-guided vascularization in engineered tissues. Heterogeneity of SLIT3 expression may underlie the variable clinical success of MSCs for tissue repair applications.

Indexed as

Tissue EngineeringTranscriptional ActivationAnimalsCell CommunicationCell MovementCluster AnalysisEndothelial CellsFemaleGene Expression ProfilingGene Expression Regulation, DevelopmentalGene Knockdown TechniquesHumansMembrane ProteinsMesenchymal Stem CellsMiceNeovascularization, PhysiologicMembrane ProteinsReceptors, Cell SurfaceROBO4 protein, humanRoundabout ProteinsSLIT3 protein, humanAngiogenesisDAPTECendothelial cellHAEChuman aortic endothelial cellhuman MSC clonal line HS-27ahuman MSC clonal line HS-5human umbilical vein endothelial cellHUVECmesenchymal stem cell or marrow stromal cellMesenchymal stem cellsMSCMSC27aMSC5N-[(3,5-Difluorophenyl)acetyl]-l-alanyl-2-phenyl]glycine-1,1-dimethyletheyl esterRevascularizationSLIT–ROBO signalingvascular endothelial growth factorVascular tissue engineeringVEGF

Identifiers

PMID24090675
PMCPMC3885335
OpenAlexW2017929060

What OpenQuestion holds

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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.