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氨基-聚乙烯醇包覆的超顺磁性氧化铁纳米颗粒适用于人骨髓间充质干细胞的体内监测。

Amino-polyvinyl alcohol coated superparamagnetic iron oxide nanoparticles are suitable for monitoring of human mesenchymal stromal cells in vivo.

机构信息

Julius Wolff Institute, Charité - Universitätsmedizin Berlin, 13353, Berlin, Germany.

出版信息

Small. 2014 Nov 12;10(21):4340-51. doi: 10.1002/smll.201400707. Epub 2014 Jul 2.

DOI:10.1002/smll.201400707
PMID:24990430
Abstract

Mesenchymal stromal cells (MSCs) are promising candidates in regenerative cell-therapies. However, optimizing their number and route of delivery remains a critical issue, which can be addressed by monitoring the MSCs' bio-distribution in vivo using super-paramagnetic iron-oxide nanoparticles (SPIONs). In this study, amino-polyvinyl alcohol coated (A-PVA) SPIONs are introduced for cell-labeling and visualization by magnetic resonance imaging (MRI) of human MSCs. Size and surface charge of A-PVA-SPIONs differ depending on their solvent. Under MSC-labeling conditions, A-PVA-SPIONs have a hydrodynamic diameter of 42 ± 2 nm and a negative Zeta potential of 25 ± 5 mV, which enable efficient internalization by MSCs without the need to use transfection agents. Transmission X-ray microscopy localizes A-PVA-SPIONs in intracellular vesicles and as cytosolic single particles. After identifying non-interfering cell-assays and determining the delivered and cellular dose, in addition to the administered dose, A-PVA-SPIONs are found to be non-toxic to MSCs and non-destructive towards their multi-lineage differentiation potential. Surprisingly, MSC migration is increased. In MRI, A-PVA-SPION-labeled MSCs are successfully visualized in vitro and in vivo. In conclusion, A-PVA-SPIONs have no unfavorable influences on MSCs, although it becomes evident how sensitive their functional behavior is towards SPION-labeling. And A-PVA-SPIONs allow MSC-monitoring in vivo.

摘要

间充质基质细胞(MSCs)是再生细胞疗法中很有前途的候选者。然而,优化其数量和输送途径仍然是一个关键问题,可以通过使用超顺磁氧化铁纳米颗粒(SPIONs)在体内监测 MSCs 的生物分布来解决。在这项研究中,引入了氨基聚(乙烯醇)包覆(A-PVA)的 SPIONs 用于细胞标记和人 MSCs 的磁共振成像(MRI)可视化。A-PVA-SPIONs 的大小和表面电荷取决于其溶剂。在 MSC 标记条件下,A-PVA-SPIONs 的水动力直径为 42±2nm,Zeta 电位为负 25±5mV,这使得 MSCs 能够高效内化,而无需使用转染剂。透射 X 射线显微镜将 A-PVA-SPIONs 定位在细胞内囊泡中和细胞质中的单个颗粒中。在确定非干扰细胞测定并确定输送和细胞剂量以及给药剂量后,发现 A-PVA-SPIONs 对 MSCs 无毒,并且对其多谱系分化潜能没有破坏作用。令人惊讶的是,MSC 迁移增加。在 MRI 中,成功地在体外和体内可视化 A-PVA-SPION 标记的 MSCs。总之,尽管 A-PVA-SPION 对 MSCs 的功能行为有明显影响,但 A-PVA-SPION 对 MSCs 没有不利影响。而且 A-PVA-SPIONs 允许在体内监测 MSC。

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