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eNOS Overexpressing Bone Marrow Cells are Safe and Effective in a Porcine Model of Myocardial Regeneration Following Acute Myocardial Infarction.
MedLine Citation:
PMID:  23837864     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIM: Cell therapy has been shown to be effective in improving LV function post myocrdial infarction (MI). We hypothesized that eNOS-transfected bone marrow cells (BMCs) are safe in a swine model of myocardial infarction (MI). We also hypothesized that endothelial nitric oxide synthase (eNOS) transfection would enhance cell function, as assessed by myocardial functional recovery post-MI.
METHODS: Fifteen female Yorkshire pigs underwent bone marrow aspiration and creation of MI. BMCs were cultured for 7 days and each pig received either autologous BMCs transiently transfected with eNOS plasmid (eNOS-BMC, n=5), non-transfected BMCs (nt-BMC, n=4) or PBS control (n=6). Cardiac MRI was performed at baseline (1 week post-MI) as well as 6 weeks post-MI.
RESULTS: There was no difference in safety outcomes between groups. Absolute left ventricular ejection fraction (LVEF) at six weeks showed a trend toward improvement in both cell therapy groups compared to baseline but worsened in the phosphate buffered saline (PBS) control group. The absolute improvement in LVEF was significantly greater in both cell therapy groups compared with PBS control. Infarct mass was significantly lower in the eNOS-BMC group between baseline and 6 weeks, but the absolute change in infarct mass was not different between groups. Finally, there was a trend toward reduced LV mass in the eNOS-BMC group.
CONCLUSIONS: BMC delivery, with and without eNOS overexpression, is safe and leads to improvement in LVEF when administered in the coronary circulation 7 days following acute MI in swine. Transfection of healthy BMCs with eNOS resulted in some improvement of left ventricular remodeling. Further study is warranted in a preclinical model that approximates the impact of cardiovascular risk factors on BMC function. This article is protected by copyright. All rights reserved.
Authors:
Michael R Ward; Kim Connelly; Ram Vijayaraghavan; Andrea K Vaags; John J Graham; Warren Foltz; Margaret R Hough; Duncan J Stewart; Alexander Dick
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-7-10
Journal Detail:
Title:  Cardiovascular therapeutics     Volume:  -     ISSN:  1755-5922     ISO Abbreviation:  Cardiovasc Ther     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-7-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101319630     Medline TA:  Cardiovasc Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
Affiliation:
LI-Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
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