Cardiac pump failure and ventricular arrhythmias represent the two major complications following myocardial infarction. Recently, cellular cardiomyoplasty has been proposed as a potential treatment option. However, this approach is still highly inefficient, because of a high initial cell loss and relatively poor cell engraftment rates.

We have therefore assessed the potential benefit of loading the cells with magnetic nanoparticles (MNPs) and providing their magnet-based positioning in the infarcted mouse heart. For this purpose bone marrow cells (BMCs), embryonic cardiomyocytes (eCMs) or ES cell-derived cardiomyocytes (ES-CMs) were loaded overnight with different types of MNPs and 200.000 of these MNP-loaded cells were injected directly into the lesion after induction of cryoinjury. During and for 10 minutes after the injection procedure a magnetic field was applied by superimposition of a custom made bar magnet (1.3 Tesla) in vicinity to the heart and to the lesion site. Two weeks after the surgical procedure left ventricular haemodynamic measurements were performed and the hearts analysed using histology.

Magnetic particle spectroscopy as well as toxicity assays identified SO-Mag5 MNPs (200 pg Fe/cell) as the best suited particles, because of their lack of toxic effects and good loading properties of all three cell types. Electron-microscopy revealed that the MNPs were enriched within autophagosomes of loaded cells.

Importantly, our transplantation experiments showed a very strong (up to 8-fold) improvement of engraftment rates for all three MNP-loaded cell types upon magneto-assisted transplantation. This finding was further corroborated by left ventricular catheterization, which yielded a significantly increased left ventricular ejection fraction (LVEF) after the transplantation of eCM.

Thus, MNP-loading of cells and their magneto-assisted intramyocardial injection strongly improve engraftment rates of the different cell types used. We are currently investigating further the mechanism(s) underlying this MNP-magnet-based improved engraftment rates. This approach could be helpful in overcoming a major technical hurdle of cellular cardiomyoplasty and in making this therapeutic direction much more efficient.