Azzabi Fahd, Rottmar Markus, Jovaisaite Virginija, Rudin Markus, Sulser Tullio, Boss Andreas, Eberli Daniel
1 Division of Urology, University Hospital Zurich , Zurich, Switzerland .
Tissue Eng Part C Methods. 2015 Feb;21(2):182-91. doi: 10.1089/ten.TEC.2014.0110. Epub 2014 Aug 4.
Cell therapies are a promising approach for the treatment of a variety of human conditions including stress urinary incontinence, but their success greatly depends on the biodistribution, migration, survival, and differentiation of the transplanted cells. Noninvasive in vivo cell tracking therefore presents an important aspect for translation of such a procedure into the clinics. Upon labeling with superparamagnetic iron oxide (SPIO) nanoparticles, cells can be tracked by magnetic resonance imaging (MRI), but possible adverse effect of the labeling have to be considered when labeling stem cells with SPIOs. In this study, human muscle precursor cells (hMPC) were labeled with increasing concentrations of SPIO nanoparticles (100-1600 μg/mL) and cell viability and differentiation capacity upon labeling was assessed in vitro. While a linear dependence between cell viability and nanoparticle concentration could be observed, differentiation capacity was not affected by the presence of SPIOs. Using a nude mouse model, a concentration (400 μg/mL) could be defined that allows reliable detection of hMPCs by MRI but does not influence myogenic in vivo differentiation to mature and functional muscle tissue. This suggests that such an approach can be safely used in a clinical setting to track muscle regeneration in patients undergoing cell therapy without negative effects on the functionality of the bioengineered muscle.
细胞疗法是治疗包括压力性尿失禁在内的多种人类疾病的一种有前景的方法,但其成功很大程度上取决于移植细胞的生物分布、迁移、存活和分化。因此,非侵入性体内细胞追踪是将此类程序转化为临床应用的一个重要方面。在用超顺磁性氧化铁(SPIO)纳米颗粒标记后,细胞可通过磁共振成像(MRI)进行追踪,但在用SPIO标记干细胞时,必须考虑标记可能产生的不良影响。在本研究中,用浓度递增的SPIO纳米颗粒(100 - 1600μg/mL)标记人肌肉前体细胞(hMPC),并在体外评估标记后细胞的活力和分化能力。虽然可观察到细胞活力与纳米颗粒浓度之间存在线性关系,但分化能力不受SPIO存在的影响。使用裸鼠模型,可以确定一个浓度(400μg/mL),该浓度能够通过MRI可靠地检测hMPC,但不影响其在体内向成熟且功能正常的肌肉组织进行成肌分化。这表明这种方法可安全用于临床环境,以追踪接受细胞治疗患者的肌肉再生情况,而不会对生物工程肌肉的功能产生负面影响。