| Intramyocardial injection of autologous cardiospheres or cardiosphere-derived cells preserves function and minimizes adverse ventricular remodeling in pigs with heart failure post-myocardial infarction. | |
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MedLine Citation:
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PMID: 21251587 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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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:
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Created Date: 2011-01-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8301365 Medline TA: J Am Coll Cardiol Country: United States |
Other Details:
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Languages: eng Pagination: 455-65 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Cedars-Sinai Heart Institute, Los Angeles, California. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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