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Novel insights into the mechanism of cell-based therapy after chronic myocardial infarction

DISCOVERIES (ISSN 2359-7232),2014, January-March

CITATION:

Schuh A, Butzbach B, Curaj A, Simsekyilmaz S, Bucur O, Kanzler I, Denecke B, Konschalla S, Kroh A, Sönmez TT, Marx N, Liehn EA. Novel insights into the mechanism of cell-based therapy after chronic myocardial infarction. Discoveries 2014, Jan-Mar; 2(1): e9.
DOI: 10.15190/d.2014.1;

Submitted: December 13, 2013; Published after revision:January 30, 2014

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Novel insights into the mechanism of cell-based therapy after chronic myocardial infarction


MD (1), MD (1,2), MD (2,3,4), PhD (2), MD (5,6), PhD (2,7), PhD (8), (2), (2,9), MD (2,10), MD (1), MD, PhD (2)*


Affiliation:
(1) Department of Cardiology and Pulmonology, Medical Faculty, RWTH Aachen University, Germany, (2) Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Germany, (3) Department of Experimental Molecular Imaging, RWTH Aachen University, Germany, (4) Victor Babes National Institute of Pathology, Bucharest, Romania, (5) Department of Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA, (6) Department of Molecular Cell Biology, Institute of Biochemistry of the Romanian Academy, Bucharest, Romania, (7) Department of Cardiothoracic and Vascular Surgery, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany, (8) Interdisciplinary Centre for Clinical Research (IZKF) Aachen, RWTH Aachen University, Aachen, Germany, (9) Department of Surgery, University Hospital Aachen, Germany, (10) Department of Oral and Maxillofacial Surgery, University Hospital Aachen, Germany

*Correspondence should be addressed to: Dr. Elisa A. Liehn, Institute for Molecular Cardiovascular Research (IMCAR); RWTH Aachen, Germany; Phone: +49 241 8035983; Fax: +49 241 8082716; Email: eliehn@ukaachen.de


Abstract


Objective: Cell transplantation therapy is considered a novel and promising strategy in regenerative medicine. Recent studies point out that paracrine effects and inflammation induced by transplanted cells are key factors for the improvement of myocardial function. The present study aims at differentiating paracrine effects from inflammatory reactions after cell transplantation.

Methods and results: Therefore, in vitro induced apoptotic bodies were transplanted after myocardial infarction in a rat model. Eight weeks after transplantation, the functional results showed no improvement in left ventricular function. Histological analysis revealed no significant differences in the amount of infiltrated cells and collagen content did not differ among the four groups, which sustains the functional data. Surprisingly, angiogenesis increased in groups with apoptotic bodies derived from HUVEC and endothelial progenitor cells, but not from fibroblasts. A complex genetic analysis of apoptotic bodies indicated that miRNAs could be responsible for these changes.

Conclusion:
Our study demonstrates that inflammation is critical for scar remodelling and improvement of the heart function after cell therapy, while neoangiogenesis alone is not sufficient to improve heart function.

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