Thorac Cardiovasc Surg 2018; 66(S 01): S1-S110
DOI: 10.1055/s-0038-1627490
Oral Presentations
Sunday, February 18, 2018
DGTHG: Basic Science: Myocardial Protection
Georg Thieme Verlag KG Stuttgart · New York

Epicardial Erythropoietin Preserves Heart Function after Myocardial Infarction through Synergistic Angiogenesis and TGF-beta/WNT Signaling Trigger in Cardiac Mesenchymal Stem Cells

C. Klopsch
1   Department of Cardiac Surgery, University of Rostock, Rostock, Germany
,
A. Skorska
1   Department of Cardiac Surgery, University of Rostock, Rostock, Germany
,
H. Lemcke
1   Department of Cardiac Surgery, University of Rostock, Rostock, Germany
,
G. Kleiner
1   Department of Cardiac Surgery, University of Rostock, Rostock, Germany
,
R. Gaebel
1   Department of Cardiac Surgery, University of Rostock, Rostock, Germany
,
M. Beyer
1   Department of Cardiac Surgery, University of Rostock, Rostock, Germany
,
R. Jaster
2   Division of Gastroenterology, Department of Medicine II, University of Rostock, Rostock, Germany
,
S. Jockenhoevel
3   Department of Tissue Engineering and Textile Implants, AME-Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany
,
B. Vollmar
4   Institute for Experimental Surgery, University of Rostock, Rostock, Germany
,
P. Dohmen
1   Department of Cardiac Surgery, University of Rostock, Rostock, Germany
,
R. David
1   Department of Cardiac Surgery, University of Rostock, Rostock, Germany
,
G. Steinhoff
1   Department of Cardiac Surgery, University of Rostock, Rostock, Germany
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Publikationsverlauf

Publikationsdatum:
22. Januar 2018 (online)

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Objectives: An early induction of intracardiac regenerative key mechanisms and angiogenesis in cardiac mesenchymal stem cells (MSCs) could enhance acute myocardial infarction (MI) healing.

Methods: Epicardial erythropoietin (EPO, 300U/kg) hydrogel was compared with intraperitoneal and intramyocardial EPO treatments after MI in rats (n = 156). Cardiac performance, EPO pharmacokinetics, cardiac tissues, early post-ischemic cardiac MSCs and human MSCs were analyzed with pressure-volume loops, immunohistochemistry, confocal laser-scanning microscopy, real-time reverse-transcription PCR, fluorescence-activated cell sorting, co-cultures, angiogenesis assays, ELISA, western-blotting and RAMAN spectroscopy, respectively.

Results: Epicardial EPO therapy after MI illustrated enhanced intracardiac regenerative key indicators (SDF-1, CXCR-4, CD34, Bcl-2, Cyclin D1, Cdc2, MMP2), augmented TGF-β/WNT signaling in cardiac MSC niches and proliferating intracardiac mesenchyme 24 hours after MI. In accordance, we found superior cardiac performance, beneficial remodeling and capillary density 6 weeks after MI. Co-cultures with neonatal cardiomyocytes revealed that EPO could support cardiomyogenic differentiation in cardiac CD45−CD44+DDR2+ MSCs. Cardiac CD45−CD44+DDR2+ MSCs and EPO demonstrated highly synergistic angiogenetic potential. Translational experiments with human MSCs confirmed TGF-β/WNT signaling in MSCs mediated by EPO and showed signs for tissue-specific differentiation capacities.

Conclusions: Epicardial EPO delivery promoted synergistic angiogenesis with cardiac post-ischemic MSCs which could have initiated improved cardiac recovery early and late after MI. Post-ischemic stimulation of mesenchymal proliferation and TGF-β/WNT signaling in intracardiac MSCs might be early effective regeneration triggers.