Shen Yunli, Liu Xuebo, Huang Zheyong, Pei Ning, Xu Jianfeng, Li Zheng, Wang Yunkai, Qian Juying, Ge Junbo
Department of Cardiology, Shanghai East Hospital, Tongji University, Shanghai, China.
Cell Transplant. 2015;24(10):1981-97. doi: 10.3727/096368914X685302. Epub 2014 Nov 5.
Magnetic targeting has the potential to enhance the therapeutic effects of stem cells through increasing retention of transplanted cells. To investigate the effects of magnetic targeting intensities on cell transplantation, we performed different magnetic intensities for mesenchymal stem cell (MSC)-targeting therapy in a rat model of ischemia/reperfusion. Rat MSCs labeled with superparamagnetic oxide nanoparticles (SPIOs) were injected into the left ventricular (LV) cavity of rats during a brief aorta and pulmonary artery occlusion. The 0.15 Tesla (T), 0.3 T, and 0.6 T magnets were placed 0∼1 mm above the injured myocardium during and after the injection of 1 × 10(6) MSCs. Fluorescence imaging and quantitative PCR revealed that magnetic targeting enhanced cell retention in the heart at 24 h in a magnetic field strength-dependent manner. Compared with the 0 T group, three magnetic targeting groups enhanced varying cell engraftment at 3 weeks, at which time LV remodeling was maximally attenuated, and the therapeutic benefit (LV ejection fraction) was also highest in the 0.3 T groups. Interestingly, due to the low MSC engraftment resulting from microvascular embolisms, the 0.6 T group failed to translate into additional therapeutic outcomes, though it had the highest cell retention. Magnetic targeting enhances cell retention in a magnetic field strength-dependent manner. However, too high of a magnetic intensity may result in microembolization and consequently undermine the functional benefits of cell transplantation.
磁靶向具有通过增加移植细胞的滞留来增强干细胞治疗效果的潜力。为了研究磁靶向强度对细胞移植的影响,我们在大鼠缺血/再灌注模型中对间充质干细胞(MSC)靶向治疗施加了不同的磁场强度。在短暂阻断主动脉和肺动脉期间,将用超顺磁性氧化物纳米颗粒(SPIOs)标记的大鼠间充质干细胞注入大鼠左心室(LV)腔。在注射1×10⁶个间充质干细胞期间及之后,将0.15特斯拉(T)、0.3 T和0.6 T的磁体放置在受损心肌上方0至1毫米处。荧光成像和定量PCR显示,磁靶向在24小时时以磁场强度依赖性方式增强了心脏中的细胞滞留。与0 T组相比,三个磁靶向组在3周时增强了不同程度的细胞植入,此时左心室重塑得到最大程度的减轻,并且在0.3 T组中治疗益处(左心室射血分数)也最高。有趣的是,由于微血管栓塞导致间充质干细胞植入率低,则0.6 T组尽管细胞滞留率最高,但未能转化为额外的治疗效果。磁靶向以磁场强度依赖性方式增强细胞滞留。然而,过高的磁场强度可能导致微栓塞,从而削弱细胞移植的功能益处。