Document Detail


Stem Cell Factor Gene Transfer Improves Cardiac Function After Myocardial Infarction in Swine.
MedLine Citation:
PMID:  25342737     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: -Stem cell factor (SCF), a ligand of the c-kit receptor, is a critical cytokine which contributes to cell migration, proliferation, and survival. It has been shown that SCF expression increases after myocardial infarction (MI) and may be involved in cardiac repair. The aim of this study was to determine whether gene transfer of membrane-bound human SCF improves cardiac function in a large animal model of MI.
METHODS AND RESULTS: -A transmural MI was created by implanting an embolic coil in the left anterior descending artery in Yorkshire pigs. One week after the MI, the pigs received direct intramyocardial injections of either a recombinant adenovirus encoding for SCF, (Ad.SCF, n=9) or β-gal (Ad.β-gal, n=6) into the infarct border area. At three months post-MI, ejection fraction increased by 12% relative to baseline after Ad.SCF therapy, whereas it decreased by 4.2% (P=0.004) in pigs treated with Ad.β-gal. Preload-recruitable stroke work was significantly higher in pigs after SCF treatment (Ad.SCF, 55.5±11.6 mmHg vs Ad.β-gal, 31.6±12.6 mmHg, P=0.005), indicating enhanced cardiac function. Histological analyses confirmed the recruitment of c-kit+ cells as well as a reduced degree of apoptosis one week after Ad.SCF injection. In addition, increased capillary density compared to pigs treated with Ad.β-gal was found at three months and suggests an angiogenic role of SCF.
CONCLUSIONS: -Local over-expression of SCF post-MI induces the recruitment of c-kit(+) cells at the infarct border area acutely. In the chronic stages, SCF gene transfer was associated with improved cardiac function in a pre-clinical model of ischemic cardiomyopathy.
Authors:
Kiyotake Ishikawa; Kenneth Fish; Jaume Aguero; Elisa Yaniz-Galende; Dongtak Jeong; Changwon Kho; Lisa Tilemann; Lauren Fish; Lifan Liang; Ahmed A Eltoukhy; Daniel G Anderson; Krisztina Zsebo; Kevin Costa; Roger J Hajjar
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-23
Journal Detail:
Title:  Circulation. Heart failure     Volume:  -     ISSN:  1941-3297     ISO Abbreviation:  Circ Heart Fail     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-24     Completed Date:  -     Revised Date:  2014-10-25    
Medline Journal Info:
Nlm Unique ID:  101479941     Medline TA:  Circ Heart Fail     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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