Document Detail


Embryonic stem cells overexpressing Pitx2c engraft in infarcted myocardium and improve cardiac function.
MedLine Citation:
PMID:  19952475     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study investigated the effects on cardiomyocyte differentiation of embryonic stem cells by the overexpression of the transcription factor, Pitx2c, and examined the effects of transplantation of these differentiated cells on cardiac function in a mouse model of myocardial infarction. Pitx2c overexpressing embryonic stem cells were characterized for cardiac differentiation by immunocytochemistry, RNA analysis, and electrophysiology. Differentiated cells were transplanted by directed injection into the infarcted murine myocardium and functional measurements of blood pressure, contractility, and relaxation were performed. Histochemistry and FISH analysis performed on these mice confirmed the engraftment and cardiac nature of the transplanted cells. Pitx2c overexpressing embryonic stem cells robustly differentiated into spontaneously contracting cells which acquired cardiac protein markers and exhibited action potentials resembling that of cardiomyocytes. These cells could also be synchronized to an external pacemaker. Significant improvements (P < 0.01) in blood pressure (56%), contractility (57%), and relaxation (59%) were observed in infarcted mice with transplants of these differentiated cells but not in mice which were transplanted with control cells. The Pitx2c overexpressing cells secrete paracrine factors which when adsorbed onto a heparinated gel and injected into the infarcted myocardium produce a comparable and significant (P < 0.01) functional recovery. Pitx2c overexpression is a valuable method for producing cardiomyocytes from embryonic stem cells, and transplantation of these cardiomyocytes into infracted myocardium restores cardiac function through multiple mechanisms.
Authors:
A K Guddati; José Javier Otero; Eric Kessler; Gary Aistrup; J Andrew Wasserstrom; Xiaoqiang Han; Matthew J Webber; Samuel I Stupp; Jon W Lomasney; John A Kessler
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International heart journal     Volume:  50     ISSN:  1349-2365     ISO Abbreviation:  Int Heart J     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-12-02     Completed Date:  2010-02-25     Revised Date:  2013-12-24    
Medline Journal Info:
Nlm Unique ID:  101244240     Medline TA:  Int Heart J     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  783-99     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Action Potentials
Animals
Calcium / analysis
Cell Differentiation
Cells, Cultured
Embryonic Stem Cells / chemistry,  physiology,  transplantation*
Female
Heart / physiology*
Immunohistochemistry
Mice
Myocardial Infarction / physiopathology,  surgery*
Myocardium / cytology
RNA / analysis
Reverse Transcriptase Polymerase Chain Reaction
Tissue Scaffolds
Transcription Factors / analysis*
Grant Support
ID/Acronym/Agency:
R01 NS020013/NS/NINDS NIH HHS; R01 NS020013-25A2/NS/NINDS NIH HHS; R01 NS020778/NS/NINDS NIH HHS; R01 NS020778-25/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Transcription Factors; 63231-63-0/RNA; SY7Q814VUP/Calcium
Comments/Corrections

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