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J. Am. Coll. Cardiol. · Apr 2015
Mechanisms of bone marrow-derived cell therapy in ischemic cardiomyopathy with left ventricular assist device bridge to transplant.
- April Stempien-Otero, Deri Helterline, Tabitha Plummer, Stephen Farris, Andrew Prouse, Nayak Polissar, Derek Stanford, and Nahush A Mokadam.
- Department of Medicine, University of Washington School of Medicine, Seattle, Washington. Electronic address: april@uw.edu.
- J. Am. Coll. Cardiol. 2015 Apr 14;65(14):1424-34.
BackgroundClinical trials report improvements in function and perfusion with direct injection of bone marrow cells into the hearts of patients with ischemic cardiomyopathy. Preclinical data suggest these cells improve vascular density, which would be expected to decrease fibrosis and inflammation.ObjectivesThe goal of this study was to test the hypothesis that bone marrow stem cells (CD34+) will improve histological measurements of vascularity, fibrosis, and inflammation in human subjects undergoing left ventricular assist device (LVAD) placement as a bridge to cardiac transplantation.MethodsSubjects with ischemic cardiomyopathy who were scheduled for placement of an LVAD as a bridge to transplantation underwent bone marrow aspiration the day before surgery; the bone marrow was processed into cell fractions (bone marrow mononuclear cells, CD34+, and CD34-). At LVAD implantation, all fractions and a saline control were injected epicardially into predetermined areas and each injection site marked. At the time of transplantation, injected areas were collected. Data were analyzed by paired Student t test comparing the effect of cell fractions injected within each subject.ResultsSix subjects completed the study. There were no statistically significant differences in complications with the procedure versus control subjects. Histological analysis indicated that myocardium injected with CD34+ cells had decreased density of endothelial cells compared to saline-injected myocardium. There were no significant differences in fibrosis or inflammation between groups; however, density of activated fibroblasts was decreased in both CD34+ and CD34- injected areas.ConclusionsTissue analysis does not support the hypothesis that bone marrow-derived CD34+ cells promote increased vascular tissue in humans with ischemic cardiomyopathy via direct injection.Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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