| Transduction of Wnt11 promotes mesenchymal stem cell transdifferentiation into cardiac phenotypes. | |
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MedLine Citation:
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PMID: 21231807 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Transplantation of mesenchymal stem cells (MSCs) has emerged as a potential treatment for ischemic heart repair. Previous studies have suggested that Wnt11 plays a critical role in cardiac specification and morphogenesis. In this study, we examined whether transduction of Wnt11 directly increases MSC differentiation into cardiac phenotypes. MSCs harvested from rat bone marrow were transduced with both Wnt11 and green fluorescent protein (GFP) (MSC(Wnt11)) using the murine stem cell virus (pMSCV) retroviral expression system; control cells were only GFP-transfected (MSC(Null)). Compared with control cells, MSC(Wnt11) was shown to have higher expression of Wnt11 by immunofluorescence, real-time polymerase chain reaction, and western blotting. MSC(Wnt11) shows a higher expression of cardiac-specific genes, including GATA-4, brain natriuretic peptide (BNP), islet-1, and α-actinin, after being cultured with cardiomyocytes (CMs) isolated from ventricles of neonatal (1-3 day) SD rats. Some MSC(Wnt11) were positive for α-actinin when MSCs were cocultured with native CMs for 7 days. Electron microscopy further confirmed the appearance of sarcomeres in MSC(Wnt11). Connexin 43 was found between GFP-positive MSCs and neonatal rat CMs labeled with red fluorescent probe PKH26. The transdifferentiation rate was significantly higher in MSC(Wnt11) than in MSC(Null), as assessed by flow cytometry. Functional studies indicated that the differentiation of MSC(Wnt11) was diminished by knockdown of GATA-4 with GATA-4-siRNA. Transduction of Wnt11 into MSCs increases their differentiation into CMs by upregulating GATA-4. |
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Authors:
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Zhisong He; Hongxia Li; Shi Zuo; Zeeshan Pasha; Yigang Wang; Yueting Yang; Wenping Jiang; Muhammad Ashraf; Meifeng Xu |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-02-26 |
Journal Detail:
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Title: Stem cells and development Volume: 20 ISSN: 1557-8534 ISO Abbreviation: Stem Cells Dev. Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-09-29 Completed Date: 2012-01-18 Revised Date: 2013-03-27 |
Medline Journal Info:
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Nlm Unique ID: 101197107 Medline TA: Stem Cells Dev Country: United States |
Other Details:
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Languages: eng Pagination: 1771-8 Citation Subset: IM |
Affiliation:
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Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio 45267, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Markers / metabolism Cell Fusion Cell Transdifferentiation* GATA4 Transcription Factor / metabolism Gene Expression Regulation Male Mesenchymal Stromal Cells / cytology*, metabolism, ultrastructure Mice Muscle Development Myocardium / cytology* Myocytes, Cardiac / cytology, metabolism, ultrastructure Phenotype Rats Rats, Sprague-Dawley Transduction, Genetic / methods* Wnt Proteins / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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HL083236/HL/NHLBI NIH HHS; HL087246/HL/NHLBI NIH HHS; HL105176/HL/NHLBI NIH HHS; R01 HL083236-05/HL/NHLBI NIH HHS; R01 HL087246-05/HL/NHLBI NIH HHS; R01 HL105176-02/HL/NHLBI NIH HHS; R01 HL110740/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/GATA4 Transcription Factor; 0/Wnt Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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