Document Detail


Intramyocardial injection of autologous cardiospheres or cardiosphere-derived cells preserves function and minimizes adverse ventricular remodeling in pigs with heart failure post-myocardial infarction.
MedLine Citation:
PMID:  21251587     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: The purpose of this study was to test the safety and efficacy of direct injection of cardiosphere-derived cells (CDCs) and their 3-dimensional precursors, cardiospheres, for cellular cardiomyoplasty in a mini-pig model of heart failure after myocardial infarction.
BACKGROUND: Intracoronary administration of CDCs has been demonstrated to reduce infarct size and improve hemodynamic indexes in the mini-pig model, but intramyocardial injection of CDCs or cardiospheres has not been assessed in large animals.
METHODS: Autologous cardiospheres or CDCs grown from endomyocardial biopsies were injected through thoracotomy 4 weeks after anteroseptal myocardial infarction. Engraftment optimization with luciferase-labeled CDCs guided the choice of cell dose (0.5 million cells/site) and target tissue (20 peri-infarct sites). Pigs were randomly allocated to placebo (n = 11), cardiospheres (n = 8), or CDCs (n = 10). Functional data were acquired before injection and again 8 weeks later, after which organs were harvested for histopathology.
RESULTS: Beyond the immediate perioperative period, all animals survived to protocol completion. Ejection fraction was equivalent at baseline, but at 8 weeks was higher than placebo in both of the cell-treated groups (placebo vs. CDC, p = 0.01; placebo vs. cardiospheres, p = 0.01). Echocardiographic and hemodynamic indexes of efficacy improved disproportionately with cardiospheres; likewise, adverse remodeling was more attenuated with cardiospheres than with CDCs. Provocative electrophysiologic testing showed no differences among groups, and no tumors were found.
CONCLUSIONS: Dosage-optimized direct injection of cardiospheres or CDCs is safe and effective in preserving ventricular function in porcine ischemic cardiomyopathy. Although CDCs and cardiospheres have equivalent effects on left ventricular ejection fraction, cardiospheres are superior in improving hemodynamics and regional function, and in attenuating ventricular remodeling.
Authors:
Shuo-Tsan Lee; Anthony J White; Satoshi Matsushita; Konstantinos Malliaras; Charles Steenbergen; Yiqiang Zhang; Tao-Sheng Li; John Terrovitis; Kristine Yee; Sinan Simsir; Raj Makkar; Eduardo Marbán
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  57     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-21     Completed Date:  2011-03-04     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  455-65     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Disease Models, Animal
Female
Heart Failure / etiology,  mortality,  surgery*
Injections, Intralesional
Mesenchymal Stem Cell Transplantation / methods*
Myocardial Infarction / complications*
Myocytes, Cardiac / transplantation*
Random Allocation
Reference Values
Risk Factors
Stroke Volume
Survival Rate
Swine
Swine, Miniature
Thoracostomy / methods
Transplantation, Autologous
Treatment Outcome
Ventricular Remodeling / physiology*
Grant Support
ID/Acronym/Agency:
U01 HL081028/HL/NHLBI NIH HHS
Comments/Corrections
Comment In:
J Am Coll Cardiol. 2011 Jan 25;57(4):466-8   [PMID:  21251588 ]

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


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