Journal
JOURNAL OF SURGICAL RESEARCH
Volume 185, Issue 1, Pages 70-83Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jss.2013.05.084
Keywords
Ischemic heart disease infarction; Cell therapy; Heart; Placenta cells; Angiogenesis
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Funding
- German Bundesministerium fur Bildung und Forschung (BMBF) [FKZ 01GN0948]
- Deutsche Forschungsgemeinschaft (DFG) through the Berlin-Brandenburg School for Regenerative Therapies [FKZ GSC 203]
- Charite Universitatsmedizin [FKZ 1315848A]
- Helmholtz-Zentrum Geesthacht [FKZ 1315848B]
- BMBF [FKZ 0315848A]
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Background: Autologous cells for cell therapy of ischemic cardiomyopathy often display age- and disease-related functional impairment, whereas an allogenic immunotolerant cell product would allow off-the-shelf application of uncompromised donor cells. We investigated the cardiac regeneration potential of a novel, clinical-grade placenta-derived human stromal cell product (PLX-PAD). Methods: PLX-PAD cells derived from human donor placentas and expanded in a three-dimensional bioreactor system were tested for surface marker expression, proangiogenic, anti-inflammatory, and immunomodulatory properties in vitro. In BALB/C mice, the left anterior descending artery was ligated and PLX-PAD cells (n = 10) or vehicle (n = 10) were injected in the infarct border zone. Four weeks later, heart function was analyzed by two-dimensional and M-mode echocardiography. Scar size, microvessel density, extracellular matrix composition, myocyte apoptosis, and PLX-PAD cell retention were studied by histology. Results: In vitro, PLX-PAD cells displayed both proangiogenesis and anti-inflammatory properties, represented by the secretion of both vascular endothelial growth factor and angiopoietin-1 that was upregulated by hypoxia, as well as by the capacity to suppress T-cell proliferation and augment IL-10 secretion when co-cultured with peripheral blood mononuclear cells. Compared with control mice, PLX-PAD-treated hearts had better contractile function, smaller infarct size, greater regional left ventricular wall thickness, and less apoptosis after 4 wk. PLX-PAD stimulated both angiogenesis and arteriogenesis in the infarct border zone, and periostin expression was upregulated in PLX-PAD-treated hearts. Conclusions: Clinical-grade PLX-PAD cells exert beneficial effects on ischemic myocardium that are associated with improved contractile function, and may be suitable for further evaluation aiming at clinical pilot trials of cardiac cell therapy. (C) 2013 Elsevier Inc. All rights reserved.
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