Universität zu Köln

Roy, Rajika, Brodarac, Andreja, Kukucka, Marian ORCID: 0000-0001-6201-1600, Kurtz, Andreas ORCID: 0000-0003-3301-6546, Becher, Peter Moritz, Juelke, Kerstin, Choi, Yeong-Hoon, Pinzur, Lena, Chajut, Ayelet, Tschoepe, Carsten and Stamm, Christof (2013). Cardioprotection by placenta-derived stromal cells in a murine myocardial infarction model. J. Surg. Res., 185 (1). S. 70 - 84. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1095-8673

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Roy, Rajika UNSPECIFIED UNSPECIFIED UNSPECIFIED Brodarac, Andreja UNSPECIFIED UNSPECIFIED UNSPECIFIED Kukucka, Marian UNSPECIFIED orcid.org/0000-0001-6201-1600 UNSPECIFIED Kurtz, Andreas UNSPECIFIED orcid.org/0000-0003-3301-6546 UNSPECIFIED Becher, Peter Moritz UNSPECIFIED UNSPECIFIED UNSPECIFIED Juelke, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Choi, Yeong-Hoon UNSPECIFIED UNSPECIFIED UNSPECIFIED Pinzur, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Chajut, Ayelet UNSPECIFIED UNSPECIFIED UNSPECIFIED Tschoepe, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Stamm, Christof UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-473018
DOI:	10.1016/j.jss.2013.05.084
Journal or Publication Title:	J. Surg. Res.
Volume:	185
Number:	1
Page Range:	S. 70 - 84
Date:	2013
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	1095-8673
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MESENCHYMAL STEM-CELLS; MARROW MONONUCLEAR-CELLS; AMNIOTIC EPITHELIAL-CELLS; UMBILICAL-CORD BLOOD; LONG-TERM BENEFITS; INTRAMYOCARDIAL DELIVERY; RETINOIC ACID; PLX-PAD; IN-VIVO; HEART Multiple languages Surgery Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47301