Document Detail


Transduction of Wnt11 promotes mesenchymal stem cell transdifferentiation into cardiac phenotypes.
MedLine Citation:
PMID:  21231807     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Zhisong He; Hongxia Li; Shi Zuo; Zeeshan Pasha; Yigang Wang; Yueting Yang; Wenping Jiang; Muhammad Ashraf; Meifeng Xu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-02-26
Journal Detail:
Title:  Stem cells and development     Volume:  20     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-29     Completed Date:  2012-01-18     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1771-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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:
HL083236/HL/NHLBI NIH HHS; HL087246/HL/NHLBI NIH HHS; HL105176/HL/NHLBI NIH HHS; R01 HL083236/HL/NHLBI NIH HHS; R01 HL083236-05/HL/NHLBI NIH HHS; R01 HL087246/HL/NHLBI NIH HHS; R01 HL087246-05/HL/NHLBI NIH HHS; R01 HL105176/HL/NHLBI NIH HHS; R01 HL105176-02/HL/NHLBI NIH HHS; R01 HL110740/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/GATA4 Transcription Factor; 0/Wnt Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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