Document Detail


Effects of cardiotrophin-1 on differentiation and maturation of rat bone marrow mesenchymal stem cells induced with 5-azacytidine in vitro.
MedLine Citation:
PMID:  19269704     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Cardiotrophin-1 (CT-1) is a cytokine involved in the growth and survival of cardiac cells that stimulates cardiomyogenesis in pluripotent murine embryonic stem (ES) cells. But it is not known whether CT-1 is responsible for the fate of differentiated bone marrow mesenchymal stem cells (BMMSCs).
METHODS: We investigated the effects of CT-1 on differentiation and maturation of BMMSCs in vitro induced with 5-azacytidine. BMMSCs isolated from femur of rats were induced by CT-1 only, by 5-azacytidine with or without CT-1,and an untreated control group was also set. After 4 weeks of induced culturing, we observed the levels of alpha-cardiac actin and troponin-I by immunohistochemical staining, the ultrastructure of induce-cultured BMMSCs, and the expression of GATA4, Nkx2.5, beta-myosin heavy chain (beta-MHC) and alpha-cardiac actin mRNA by real time RT-PCR analysis.
RESULTS: Differentiated BMMSCs treated by 5-azacytidine and CT-1 distinctly showed formations of myofilaments and myotube-like structures-morphological characteristics of myocyte like cells, and spontaneous contraction of a few cells was observed. The protein levels of alpha-cardiac actin and troponin-T were significantly higher than control. Furthermore, mRNA expression of GATA4, Nkx2.5, alpha-cardiac actin and beta-MHC was increased remarkably.
CONCLUSIONS: This study suggests that induced culturing of BMMSCs in the presence of 5-azacytidine combined with CT-1 can enhance cardiomyocytic characteristics. CT-1 upregulates the expression of GATA4, Nkx2-5, alpha-cardiac actin and beta-MHC mRNA, and rapidly promotes the differentiation and maturation of cardiomyocyte-like cells differentiated from BMMSCs induced with 5-azacytidine.
Authors:
Chen Xinyun; Zeng Zhi; Zhou Bin; Rao Li; Chen Yucheng; Yan Yafei; Zhang Tingjie; Li Shengfu
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Publication Detail:
Type:  In Vitro; Journal Article     Date:  2009-03-09
Journal Detail:
Title:  International journal of cardiology     Volume:  143     ISSN:  1874-1754     ISO Abbreviation:  Int. J. Cardiol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-23     Completed Date:  2010-12-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  171-7     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Department of Cardiology, West China Hospital, Sichuan University, Chengdu 610041, China.
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MeSH Terms
Descriptor/Qualifier:
Actins / genetics
Animals
Azacitidine / pharmacology*
Bone Marrow Cells / cytology,  drug effects
Cell Differentiation / drug effects
Cell Survival / drug effects
Cells, Cultured
Cytokines / pharmacology*
Enzyme Inhibitors / pharmacology
GATA4 Transcription Factor / genetics
Gene Expression / drug effects
Homeodomain Proteins / genetics
Male
Mesenchymal Stem Cells / cytology*,  drug effects*
Myosin Heavy Chains / genetics
Rats
Rats, Sprague-Dawley
Transcription Factors / genetics
Chemical
Reg. No./Substance:
0/Actins; 0/Bmyo protein, rat; 0/Cytokines; 0/Enzyme Inhibitors; 0/GATA4 Transcription Factor; 0/Gata4 protein, rat; 0/Homeodomain Proteins; 0/Myosin Heavy Chains; 0/Nkx2.5 protein, rat; 0/Transcription Factors; 0/cardiotrophin 1; 320-67-2/Azacitidine

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