Evidence map›Paper›PMID 23517131›Full record

ArticleStem cells and development2013

Human embryonic stem cell-derived cardiomyocytes migrate in response to gradients of fibronectin and Wnt5a.

Kara White Moyes, Christopher G Sip, Willimark Obenza, Emily Yang, Cody Horst, Robert E Welikson, Stephen D Hauschka, Albert Folch, Michael A Laflamme

Abstract read
In one paragraph

Article in Stem cells and development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

18 citing papers in PubMed, 28 citations in OpenAlex.

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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 2 institutions in 1 country.

Kara White MoyesInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
Christopher G Sip
Willimark Obenza
Emily Yang
Cody Horst
Robert E Welikson
Stephen D Hauschka
Albert Folch
Michael A Laflamme
University of Washington · USVirginia Mason Medical Center · US

Funding

Progenitor Cell Biology Consortium Administrative Coordinating CenterU01HL099997 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI TERRIN, MICHAEL L · 2009 to 2015
$29.9M
Vascularization and Growth of Human Myocardial GraftsP01HL094374 · NHLBI · UNIVERSITY OF WASHINGTON · PI MINAMI, ELINA · 2010 to 2014
$14.5M
Engineered Cardiac Morphogenesis-Stem Cells and ScaffoldsR01HL064387 · NHLBI · UNIVERSITY OF WASHINGTON · PI RATNER, BUDDY D · 2006 to 2010
$10.2M
CARDIOVASCULAR RESEARCH TRAINING PROGRAMT32HL007828 · NHLBI · UNIVERSITY OF WASHINGTON · PI Francis Kim, Farid Moussavi-Harami · 1997 to 2026
$10.2M
Multiplexed Microfluidic Gradients for Axon GuidanceR01NS064387 · NINDS · UNIVERSITY OF WASHINGTON · PI FOLCH, ALBERT · 2011 to 2015
$1.6M
NHLBI NIH HHS P01 HL094374NHLBI NIH HHS P01-HL094374NHLBI NIH HHS R01-HL064387NHLBI NIH HHS T32 HL007828NHLBI NIH HHS U01-HL099997NINDS NIH HHS R01 NS064387
6 · The paper itself

Abstract

An improved understanding of the factors that regulate the migration of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) would provide new insights into human heart development and suggest novel strategies to improve their electromechanical integration after intracardiac transplantation. Since nothing has been reported as to the factors controlling hESC-CM migration, we hypothesized that hESC-CMs would migrate in response to the extracellular matrix and soluble signaling molecules previously implicated in heart morphogenesis. To test this, we screened candidate factors by transwell assay for effects on hESC-CM motility, followed by validation via live-cell imaging and/or gap-closure assays. Fibronectin (FN) elicited a haptotactic response from hESC-CMs, with cells seeded on a steep FN gradient showing nearly a fivefold greater migratory activity than cells on uniform FN. Studies with neutralizing antibodies indicated that adhesion and migration on FN are mediated by integrins α-5 and α-V. Next, we screened 10 soluble candidate factors by transwell assay and found that the noncanonical Wnt, Wnt5a, elicited an approximately twofold increase in migration over controls. This effect was confirmed using the gap-closure assay, in which Wnt5a-treated hESC-CMs showed approximately twofold greater closure than untreated cells. Studies with microfluidic-generated Wnt5a gradients showed that this factor was chemoattractive as well as chemokinetic, and Wnt5a-mediated responses were inhibited by the Frizzled-1/2 receptor antagonist, UM206. In summary, hESC-CMs show robust promigratory responses to FN and Wnt5a, findings that have implications on both cardiac development and cell-based therapies.

Indexed as

Antibodies, NeutralizingCell AdhesionCell DifferentiationCell MovementDiffusion Chambers, CultureEmbryonic Stem CellsExtracellular MatrixFibronectinsGene ExpressionHumansMolecular ImagingMyocytes, CardiacProto-Oncogene ProteinsReceptors, FibronectinSignal TransductionWnt-5a ProteinAntibodies, NeutralizingFibronectinsProto-Oncogene ProteinsReceptors, FibronectinWnt-5a ProteinWNT5A protein, humanWnt Proteins

Identifiers

PMID23517131
PMCPMC3732016
OpenAlexW2135820025

What OpenQuestion holds

Textmetadata
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.