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 nanoparticles (MNP) loading of fluorescent 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.

心脏中的细胞置换被认为是治疗梗塞后心力衰竭的有前途的策略。直接心肌内注射细胞被证明是最有效的应用途径，但是，植入率非常低（<5％），严重阻碍了其功效。在本文中，我们结合了应用荧光粉来增强荧光胚胎心肌细胞（eCM）和胚胎干细胞衍生的心肌细胞（ES-CM）的磁性纳米颗粒（MNP），以增强它们的短期和长期植入。为了优化梗塞区域内细胞MNP的吸收和磁力，首先在体外进行了数值模拟和实验。所有测试的细胞类型均可有效加载SOMag5-MNP（200 pg /细胞）而无毒副作用。在距心脏5毫米的距离处应用1.3 T磁体10分钟，分别在治疗后2周和2周时将eCM和ES-CM的植入率提高了约7倍，在8周时提高了3.4倍（eCM）的植入率，并且还大大改善了左心室在所有时间点都起作用。作为潜在的机制，我们发现磁场的施加阻止了细胞通过注入通道的初始急剧损失。此外，嫁接的eCM表现出更高的增殖和更低的细胞凋亡率。电子显微镜显示，在经过磁处理的移植物中，植入的eCM具有更好的分化能力，细胞与细胞之间的接触形成以及更多的生理基质形成。基因表达数据证实了这些结果。因此，