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Superparamagnetic iron oxide nanoparticles for direct labeling of stem cells and in vivo MRI tracking.
Contrast Media & Molecular Imaging Pub Date : 2015-08-04 , DOI: 10.1002/cmmi.1658
Saejeong J Kim 1 , Bobbi Lewis 1 , Mark-Steven Steiner 2 , Ursula V Bissa 2 , Christian Dose 2 , Joseph A Frank 1, 3
Affiliation  

To develop effective stem cell therapies, it is important to track therapeutic cells non-invasively and monitor homing to areas of pathology. The purpose of this study was to design and evaluate the labeling efficiency of commercially available dextran-coated superparamagnetic iron oxide nanoparticles, FeraTrack Direct (FTD), in various stem and immune cells; assess the cytotoxicity and tolerability of the FTD in stem cells; and monitor stem cell homing using FTD-labeled bone-marrow-derived mesenchymal stromal cells (BMSCs) and neural stem cells (NSCs) in a tumor model by in vivo MRI. BMSCs, NSCs, hematopoietic stem cells (HSCs), T-lymphocytes, and monocytes were labeled effectively with FTD without the need for transfection agents, and Prussian blue (PB) staining and transmission electron microscopy (TEM) confirmed intracellular uptake of the agent. The viability, proliferation, and functionality of the labeled cells were minimally or not affected after labeling. When 10(6) FTD-labeled BMSCs or NSCs were injected into C6 glioma bearing nude mice, the cells homing to the tumors were detected as hypointense regions within the tumor using 3 T clinical MRI up to 10 days post injection. Histological analysis confirmed the homing of injected cells to the tumor by the presence of PB positive cells that are not macrophages. Labeling of stem cells or immune cells with FTD was non-toxic, and should facilitate the translation of this agent to clinical trials for evaluation of trafficking of cells by MRI.

中文翻译:

超顺磁性氧化铁纳米颗粒,用于干细胞的直接标记和体内MRI跟踪。

为了开发有效的干细胞疗法,重要的是无创地跟踪治疗细胞并监测归巢到病理区域。这项研究的目的是设计和评估可商购的葡聚糖包被的超顺磁性氧化铁纳米颗粒FeraTrack Direct(FTD)在各种干细胞和免疫细胞中的标记效率;评估FTD在干细胞中的细胞毒性和耐受性;并通过体内MRI在肿瘤模型中使用FTD标记的骨髓间充质基质细胞(BMSC)和神经干细胞(NSC)监测干细胞归巢。使用FTD有效标记BMSC,NSC,造血干细胞(HSC),T淋巴细胞和单核细胞,而无需转染剂,普鲁士蓝(PB)染色和透射电镜(TEM)证实了该药物在细胞内的吸收。标记后,标记细胞的活力,增殖和功能受到的影响很小或没有受到影响。当将10(6)FTD标记的BMSC或NSC注射到带有C6胶质瘤的裸鼠体内时,直至注射后10天,使用3 T临床MRI可以将归巢于肿瘤的细胞检测为肿瘤内的低血脂区域。组织学分析证实了不是巨噬细胞的PB阳性细胞的存在将注射的细胞归巢于肿瘤。用FTD标记干细胞或免疫细胞是无毒的,应有助于将该试剂翻译为临床试验,以通过MRI评估细胞的运输。标记后,标记细胞的功能和功能微乎其微或不受影响。当将10(6)FTD标记的BMSC或NSC注射到带有C6胶质瘤的裸鼠体内时,直至注射后10天,使用3 T临床MRI可以将归巢于肿瘤的细胞检测为肿瘤内的低血脂区域。组织学分析证实了注射的细胞归因于不是巨噬细胞的PB阳性细胞的归巢。用FTD标记干细胞或免疫细胞是无毒的,应有助于将该试剂翻译为临床试验,以通过MRI评估细胞的运输。标记后,标记细胞的功能和功能微乎其微或不受影响。当将10(6)FTD标记的BMSC或NSC注射到带有C6胶质瘤的裸鼠体内时,直至注射后10天,使用3 T临床MRI可以将归巢于肿瘤的细胞检测为肿瘤内的低血脂区域。组织学分析证实了注射的细胞归因于不是巨噬细胞的PB阳性细胞的归巢。用FTD标记干细胞或免疫细胞是无毒的,应有助于将该试剂翻译为临床试验,以通过MRI评估细胞的运输。直至注射后10天,使用3 T临床MRI将归巢于肿瘤的细胞检测为肿瘤内的低丘脑区域。组织学分析证实了注射的细胞归因于不是巨噬细胞的PB阳性细胞的归巢。用FTD标记干细胞或免疫细胞是无毒的,应有助于将该试剂翻译为临床试验,以通过MRI评估细胞的运输。直至注射后10天,使用3 T临床MRI将归巢于肿瘤的细胞检测为肿瘤内的低丘脑区域。组织学分析证实了注射的细胞归因于不是巨噬细胞的PB阳性细胞的归巢。用FTD标记干细胞或免疫细胞是无毒的,应有助于将该试剂翻译为临床试验,以通过MRI评估细胞的运输。
更新日期:2019-11-01
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