Zugriffsnummer 40108
Dokumenttyp Zeitschriftenartikel
Peer Review mit Peer Review
Sprache Englisch
Titel Improved heart repair upon myocardial infarction: Combination of magnetic nanoparticles and tailored magnets strongly increases engraftment of myocytes
Autor(in); Institution
Ottersbach, A.; Department of Cardiac Surgery, Medical Faculty, University of Bonn, Bonn, GERMANY; Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, Bonn, GERMANY
Mykhaylyk, O.; Institute of Molecular Immunology/ Experimental Oncology, Klinikum München rechts der Isar, Technische Universität München, München, GERMANY
Heidsieck, A.; Institute of Medical Engineering (IME.TUM), Garching b. München, GERMANY
Eberbeck, Dietmar; 8.2, Biosignale, PTB-Berlin
Rieck, S.; Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, Bonn, GERMANY
Zimmermann, K.; Institute of Pharmacology and Toxicology, Medical Faculty, University of Bonn, Bonn, GERMANY
Breitbach, M.; Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, Bonn, GERMANY
Engelbrecht, B.; Department of Cardiac Surgery, Medical Faculty, University of Bonn, Bonn, GERMANY
Brügmann, T.; Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, Bonn, GERMANY
Hesse, M.; Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, Bonn, GERMANY
Welz, A.; Department of Cardiac Surgery, Medical Faculty, University of Bonn, Bonn, GERMANY
Sasse, P; Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, Bonn, GERMANY
Wenzel, D.; Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, Bonn, GERMANY
Plank, C.; Institute of Molecular Immunology/ Experimental Oncology, Klinikum München rechts der Isar, Technische Universität München, München, GERMANY
Gleich, B.; Institute of Medical Engineering (IME.TUM), Garching b. München, GERMANY
Hölzel, M.; Unit for RNA Biology, Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, GERMANY
Bloch, W.; Institute of Cardiovascular Research and Sport Medicine, Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Cologne, GERMANY
Pfeifer, A.; Institute of Pharmacology and Toxicology, Medical Faculty, University of Bonn, Bonn, GERMANY
Fleischmann, B. K.; Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, Bonn, GERMANY
Roell, W.; Department of Cardiac Surgery, Medical Faculty, University of Bonn, Bonn, GERMANY
Quelle/Jahr Biomaterials: 155 (2017), 176 - 190
ISSN 0142-9612 (PRINT) ; 1878-5905 (ONLINE)
DOI
Verlag Amsterdam [u.a.]: Elsevier
Freie Schlagworte Magnetic nanoparticles ; Myocardial infarction ; Cell transplantation ; Magnetic attraction ; Magnetic nanoparticle cell loading
Zusammenfassung Cell replacement in the heart is considered a promising strategy for the treatment of post-infarct heart failure. Direct intramyocardial injection of cells proved to be the most effective application route, however, engraftment rates are very low (<5%) strongly hampering its efficacy. Herein we combine magnetic nanoparticle (MNP) loading of EGFP labeled embryonic cardiomyocytes (eCM) and embryonic stem cell-derived cardiomyocytes (ES-CM) with application of custom designed magnets to enhance their short and long-term engraftment. To optimize cellular MNP uptake and magnetic force within the infarct area, first numerical simulations and experiments were performed in vitro. All tested cell types could be loaded efficiently with SOMag5-MNP (200 pg/cell) without toxic side effects. Application of a 1.3 T magnet at 5 mm distance from the heart for 10 min enhanced engraftment of both eCM and ES-CM by approximately 7 fold at 2 weeks and 3.4 fold (eCM) at 8 weeks after treatment respectively and also strongly improved left ventricular function at all time points. As underlying mechanisms we found that application of the magnetic field prevented the initial dramatic loss of cells via the injection channel. In addition, grafted eCM displayed higher proliferation and lower apoptosis rates. Electron microscopy revealed better differentiation of engrafted eCM, formation of cell to cell contacts and more physiological matrix formation in magnet-treated grafts. These results were corroborated by gene expression data. Thus, combination of MNP-loaded cells and magnet-application strongly increases long-term engraftment of cells addressing a major shortcoming of cardiomyoplasty.

Zitierung

Ottersbach, A., Mykhaylyk, O., Heidsieck, A., Eberbeck, D., Rieck, S., Zimmermann, K., Breitbach, M., Engelbrecht, B., Brügmann, T., Hesse, M., Welz, A., Sasse, P., Wenzel, D., Plank, C., Gleich, B., Hölzel, M., Bloch, W., Pfeifer, A., Fleischmann, B. K., & Roell, W. (2017). Improved heart repair upon myocardial infarction: Combination of magnetic nanoparticles and tailored magnets strongly increases engraftment of myocytes. Biomaterials, 155, 176–190. https://doi.org/10.1016/j.biomaterials.2017.11.012

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