MRI of iron oxide nanoparticle-labeled ADSCs in a model of hindlimb ischemia
MRI of iron oxide nanoparticle-labeled ADSCs in a model of hindlimb ischemia
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DOI：
10.1016/j.biomaterials.2013.03.014
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发表时间：
2013-07-01
期刊：
影响因子：
14
通讯作者：
Lu, Xinwu
中科院分区：
文献类型：
--
作者：
Qin, Jinbao;Li, Kangan;Lu, Xinwu
脂肪源性干细胞（ADSCs）在缺血性疾病的修复中显示出巨大的潜力。然而，对标记的脂肪干细胞的命运，迁移，分化和体内分布的研究很少报道。本研究设计、合成了磁性氧化铁纳米粒子，并将其与内消旋-2，3-二巯基丁二酸（DMSA）包覆，制备了DMSA纳米粒子（DMSA-NPs）。评价DMSA-NP的性质、尺寸分布和表征。获得表达绿色荧光蛋白的ADSC（GFP-ADSC）并用DMSA-NP标记。体外检测标记的GFP-ADSCs的活力、细胞毒性和多向分化能力。将标记和未标记的GFP-ADSCs注射到小鼠后肢缺血模型中，并获得3 T磁共振成像（MRI）。合成的DMSA-NPs在体外和体内有效地标记GFP-ADSCs，而不影响细胞活力、增殖、细胞周期和多分化能力。MM在标记的GFP-ADSC中显示持续长达8周的低信号斑点。普鲁士蓝染色和免疫荧光检测显示，标记的GFP-ADSCs分布于缺血区及其周围，部分分化为毛细血管。这一观察结果与未标记细胞移植的观察结果相同。标记的细胞也主要在肝脏和脾脏中被发现，在肺、肠、心脏和肾脏中的数量明显较少。开发的DMSA-NP显示出相当大的潜力，可用作干细胞MM的纳米探针，这将增强我们对缺血性疾病基于细胞的治疗策略的理解。(C)2013爱思唯尔有限公司保留所有权利。
Adipose-derived stem cells (ADSCs) exhibit tremendous potential for repair of ischemic diseases. However, studies on the fate, migration, differentiation, and body distribution of the labeled ADSCs are rarely reported. In this study, magnetic iron oxide nanoparticles were designed, synthesized, and coated with meso-2,3-dimercaptosuccinic acid (DMSA) to produce DMSA nanoparticles (DMSA-NPs). The properties, size distribution, and characterization of DMSA-NPs were evaluated. Green fluorescent protein expressing ADSCs (GFP-ADSCs) were obtained and labeled with DMSA-NPs. The viability, cytotoxicity and multi-differentiation capacity of labeled GFP-ADSCs were evaluated in vitro. Labeled and non-labeled GFP-ADSCs were injected into a mouse model of hindlimb ischemia, and 3T magnetic resonance imaging (MRI) was acquired. The synthesized DMSA-NPs efficiently labeled the GFP-ADSCs in vitro and in vivo without affecting cell viability, proliferation, cell cycle, and multi-differentiation capacity. The MM showed hypointense spots in the labeled GFP-ADSCs that lasted up to 8 weeks. Prussian blue staining and immunofluorescence assay at 4 and 8 weeks indicated that the labeled GFP-ADSCs were in and around the ischemic sites and some differentiated into capillaries. This observation is identical to that seen for transplants of unlabeled cells. Labeled cells were also identified mainly in the liver and spleen, with significantly smaller amounts in the lungs, intestines, heart, and kidney. Developed DMSA-NPs were shown to exhibit a considerable potential for use as nanoprobes for MM of stem cells, which will enhance our understanding of cell-based therapeutic strategies for ischemic diseases. (C) 2013 Elsevier Ltd. All rights reserved.