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Text
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URL Address
<a href="http://doi.org/10.1161/CIRCULATIONAHA.111.082453" target="_blank" rel="noreferrer noopener">http://doi.org/10.1161/CIRCULATIONAHA.111.082453</a>
Pages
314–324
Issue
3
Volume
126
Dublin Core
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Title
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Myocardial CXCR4 expression is required for mesenchymal stem cell mediated repair following acute myocardial infarction.
Publisher
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Circulation
Date
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2012
2012-07
Subject
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Animals; Apoptosis/physiology; Cardiac/cytology/physiology; Cell Movement/physiology; Chemokine CXCL12/*metabolism; Coronary Circulation/physiology; CXCR4/*genetics/metabolism; Gene Expression/physiology; Green Fluorescent Proteins/genetics; Inbred C57BL; Knockout; Mesenchymal Stem Cell Transplantation/*methods; Mesenchymal Stem Cells/*metabolism; Mice; Myocardial Infarction/genetics/pathology/*therapy; Myocardium/cytology; Myocytes; Paracrine Communication/physiology; Receptors; Ventricular Remodeling/physiology
Creator
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Dong Feng; Harvey James; Finan Amanda; Weber Kristal; Agarwal Udit; Penn Marc S
Description
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BACKGROUND: Overexpression of stromal cell-derived factor-1 in injured tissue leads to improved end-organ function. In this study, we quantify the local trophic effects of mesenchymal stem cell (MSC) stromal cell-derived factor-1 release on the effects of MSC engraftment in the myocardium after acute myocardial infarction. METHODS AND RESULTS: Conditional cardiac myocyte CXCR4 (CM-CXCR4) null mice were generated by use of tamoxifen-inducible cardiac-specific cre by crossing CXCR4 floxed with MCM-cre mouse. Studies were performed in littermates with (CM-CXCR4 null) or without (control) tamoxifen injection 3 weeks before acute myocardial infarction. One day after acute myocardial infarction, mice received 100,000 MSC or saline via tail vein. We show alpha-myosin heavy chain MerCreMer and the MLC-2v promoters are active in cardiac progenitor cells. MSC engraftment in wild-type mice decreased terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling positive CM (-44%, P\textless0.01), increased cardiac progenitor cell recruitment (100.9%, P\textless0.01), and increased cardiac myosin-positive area (39%, P\textless0.05) at 4, 7, and 21 days after acute myocardial infarction, respectively. MSC in wild-type mice resulted in 107.4% (P\textless0.05) increase in ejection fraction in comparison with 25.9% (P=NS) increase in CM-CXCR4 null mice. These differences occurred despite equivalent increases (16%) in vascular density in response to MSC infusion in wild-type and
Identifier
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<a href="http://doi.org/10.1161/CIRCULATIONAHA.111.082453" target="_blank" rel="noreferrer noopener">10.1161/CIRCULATIONAHA.111.082453</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2012
Agarwal Udit
Animals
Apoptosis/physiology
Cardiac/cytology/physiology
Cell Movement/physiology
Chemokine CXCL12/*metabolism
Circulation
Coronary Circulation/physiology
CXCR4/*genetics/metabolism
Department of Integrative Medical Sciences
Dong Feng
Finan Amanda
Gene Expression/physiology
Green Fluorescent Proteins/genetics
Harvey James
Inbred C57BL
Knockout
Mesenchymal Stem Cell Transplantation/*methods
Mesenchymal Stem Cells/*metabolism
Mice
Myocardial Infarction/genetics/pathology/*therapy
Myocardium/cytology
Myocytes
NEOMED College of Medicine
Paracrine Communication/physiology
Penn Marc S
Receptors
Ventricular Remodeling/physiology
Weber Kristal