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

Alexander Schuh; Britta Butzbach; Adelina Curaj; Sakine Simsekyilmaz; Octavian Bucur; Isabela Kanzler; Bernd Deneke; Simone Konschalla; Andreas Kroh; Tolga Taha Sönmez; Nikolaus Marx; Elisa A Liehn

doi:10.15190/d.2014.1

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

Discoveries (Craiova). 2014 Jan 30;2(1):e9. doi: 10.15190/d.2014.1.

Authors

Alexander Schuh¹, Britta Butzbach^{1

2}, Adelina Curaj^{2

3

4}, Sakine Simsekyilmaz², Octavian Bucur^{5

6}, Isabela Kanzler^{2

7

8}, Bernd Deneke⁹, Simone Konschalla², Andreas Kroh^{2

10}, Tolga Taha Sönmez^{2

11}, Nikolaus Marx¹, Elisa A Liehn²

Affiliations

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 Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen, Germany.
⁸ Department of Cardiothoracic and Vascular Surgery, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
⁹ Interdisciplinary Centre for Clinical Research (IZKF) Aachen, RWTH Aachen University, Aachen, Germany.
¹⁰ Department of Surgery, University Hospital Aachen, Germany.
¹¹ Department of Oral and Maxillofacial Surgery, University Hospital Aachen, Germany.

Abstract

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

Keywords: apoptotic bodies; cell therapy; mechanisms; microRNAs; myocardial infarction; transplantation.