Thorac Cardiovasc Surg 2015; 63 - OP81
DOI: 10.1055/s-0035-1544333

Site-specific Positioning of Magnetic Nanoparticle (MNP) Loaded Progenitors Improves Cell Engraftment, Long Term Myocardial Function and Protects from Ventricular Tachycardia upon Myocardial Infarction

A. Ottersbach 1, D. Eberbeck 2, T. Brügmann 1, B. Gleich 3, C. Plank 4, P. Sasse 1, A. Pfeifer 5, A. Welz 6, B.K. Fleischmann 1, W. Röll 6
  • 1Universität Bonn, Institut f. Physiologie I, Bonn, Germany
  • 2Physikalisch Technische Bundesanstalt, Berlin, Germany
  • 3TU München, IMETUM Zentralinstitut f. Medizintechnik, Garching, Germany
  • 4TU München, Institut f. experimentelle Onkologie, München, Germany
  • 5Universität Bonn, Institut f. Pharmakologie u. Toxikologie, Bonn, Germany
  • 6Universitätsklinikum Bonn, Klinik und Poliklinik für Herzchirurgie, Bonn, Germany

Objectives: In the past we showed, that magnetic field assisted transplantation of MNP loaded cells results in prominent long term cell engraftment and improvement of the left ventricular function of cryolesioned murine hearts. In the present study we have investigated the underlying mechanical and biological mechanisms as well as the effects of MNP loading on the electrophysiological characteristics of the transplanted embryonic cardiomyocytes (eCM) and the infarct zone.

Methods: EGFP-transgenic murine eCM were isolated and co-incubated with SOMag5 MNPs (200pg Fe/cell). Then, 200.000 MNP-loaded cells were injected directly into a myocardial cryolesion while applying a custom made magnet during and 10 minutes after the injection. Short and long-term distribution of the MNPs within the heart and remaining organs was investigated by magnetorelaxometry (MRX). Early postoperative fate of injected cells was investigated by caspase3, TUNEL, Ki67 and phspho-histonH3 (PHH3) staining. To elucidate potential changes of the electrophysiological characteristics following MNP loading of transplanted cells in vitro and in vivo electrophysiological testing (EPU) was performed.

Results: MRX performed 10 minutes after cell transplantation showed a constant amount of MNPs within the thoracic cavity of all mice. While after magnet application more than 50% of total MNPs were still present within the left ventricular myocardium, in control mice only ∼25% of MNPs were detected. After 2 and 8 weeks the majority of MNPs were still present within the heart, in remaining organs most of the MNPs were seen in the liver and the kidneys. Caspase 3 and TUNEL staining showed significant higher amounts of apoptotic cells in control mice. In contrast, after magnet assisted cell injection significantly more and proliferating eCM were detected by Ki67 and PHH3 staining. EPU of single cells in vitro using patch clamp techniques and in vivo performed extrastimulus- and burst-pacing revealed no changes of the electrophysiological characteristics of MNP loaded eCM and unchanged protection from ventricular tachycardia (VT).

Conclusions: Thus, MNP-loading of eCM and consecutive magneto-assisted intramyocardial cell injection strongly improves cell engraftment by short term mechanical and long lasting biological mechanisms resulting in prominent improvement of heart function. MNP use does not burden loaded cells and does not alter VT protective impact of transplanted cells.