Whole body tracking of superparamagnetic iron oxide nanoparticle-labelled cells--a rheumatoid arthritis mouse model.
Whole body tracking of superparamagnetic iron oxide nanoparticle-labelled cells--a rheumatoid arthritis mouse model.
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DOI：
10.1186/scrt337
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发表时间：
2013-10-17
影响因子：
7.5
通讯作者：
El Haj AJ
中科院分区：
文献类型：
--
作者：
Markides H;Kehoe O;Morris RH;El Haj AJ
骨髓间充质干细胞（mesenchymal stem cells，MSCs）的免疫抑制和分化能力使其在类风湿关节炎（rheumatoid arthritis，RA）治疗中的应用成为可能。评估细胞整合和生物分布的非侵入性方法是评估这种疗法的风险和成功的基础，从而实现临床转化。本文定义了使用超顺磁性氧化铁纳米粒子（SPION）结合磁共振成像（MRI）成像和跟踪骨髓间充质干细胞在体内的一个小鼠模型的RA。分离鼠MSC（mMSC），扩增并用SiMAG（市售颗粒）标记。通过用浓度范围为0至10 μg/ml的SiMAG标记mMSC并在MR成像之前将不同细胞剂量（103至5 × 105个细胞）重悬于2 mg/ml胶原中来研究体外MRI可见性阈值。类似地，通过将用0至10 μg/ml SiMAG标记的3 × 105 mMSC植入小鼠滑膜腔内并进行MR成像来确定体内检测阈值。在RA诱导后，通过关节内注射植入300，000个用SiMAG（10 μg/ml）标记的mMSC，并在7天内监测关节肿胀作为RA发展的指示。此外，研究了SiMAG对细胞活力、增殖和分化的影响。将1 μg/ml（300，000个细胞）的最小颗粒浓度和100，000个细胞（5和10 μg/ml）的细胞剂量确定为体外MRI检测阈值。细胞活力，增殖和分化能力不受影响，标记的人口经历成功分化成骨和成脂谱系。在含有SiMAG标记的和未标记的mMSC的组中测量到关节肿胀的显著降低（P < 0.01），这意味着SPION的存在不影响细胞的免疫调节特性。体内MRI扫描显示出良好的对比度，并在植入后7天内识别出滑膜关节内的SiMAG标记群体。这一点通过组织学分析得到了进一步证实。我们已经能够以非侵入性方式监测和跟踪风湿关节内干细胞群的迁移。该手稿进一步强调了SiMAG证明的关键特性（生物相容性和在临床相关系统内以实际剂量产生显著对比度的能力），这些特性应纳入新的临床批准示踪剂的设计中。
The application of mesenchymal stem cells (MSCs) in treating rheumatoid arthritis (RA) has been made possible by the immunosuppressive and differentiation abilities of these cells. A non-invasive means of assessing cell integration and bio-distribution is fundamental in evaluating the risks and success of this therapy, thereby enabling clinical translation. This paper defines the use of superparamagnetic iron oxide nanoparticles (SPIONs) in conjunction with magnetic resonance imaging (MRI) to image and track MSCs in vivo within a murine model of RA. Murine MSCs (mMSCs) were isolated, expanded and labelled with SiMAG, a commercially available particle. In vitro MRI visibility thresholds were investigated by labelling mMSCs with SiMAG with concentrations ranging from 0 to 10 μg/ml and resuspending varying cell doses (103 to 5 × 105 cells) in 2 mg/ml collagen prior to MR-imaging. Similarly, in vivo detection thresholds were identified by implanting 3 × 105 mMSCs labelled with 0 to 10 μg/ml SiMAG within the synovial cavity of a mouse and MR-imaging. Upon RA induction, 300,000 mMSCs labelled with SiMAG (10 μg/ml) were implanted via intra-articular injection and joint swelling monitored as an indication of RA development over seven days. Furthermore, the effect of SiMAG on cell viability, proliferation and differentiation was investigated. A minimum particle concentration of 1 μg/ml (300,000 cells) and cell dose of 100,000 cells (5 and 10 μg/ml) were identified as the in vitro MRI detection threshold. Cell viability, proliferation and differentiation capabilities were not affected, with labelled populations undergoing successful differentiation down osteogenic and adipogenic lineages. A significant decrease (P < 0.01) in joint swelling was measured in groups containing SiMAG-labelled and unlabelled mMSCs implying that the presence of SPIONs does not affect the immunomodulating properties of the cells. In vivo MRI scans demonstrated good contrast and the identification of SiMAG-labelled populations within the synovial joint up to 7 days post implantation. This was further confirmed using histological analysis. We have been able to monitor and track the migration of stem cell populations within the rheumatic joint in a non-invasive manner. This manuscript goes further to highlight the key characteristics (biocompatible and the ability to create significant contrast at realistic doses within a clinical relevant system) demonstrated by SiMAG that should be incorporated into the design of a new clinically approved tracking agent.
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DOI：
10.2967/jnumed.108.053546
发表时间：
2009-02
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Budde MD;Frank JA
通讯作者：
Frank JA
影响因子：
4.9
作者：
Dazzi F;van Laar JM;Cope A;Tyndall A
通讯作者：
Tyndall A
影响因子：
2.8
作者：
Henning, Tobias D.;Gawande, Rakhee;Daldrup-Link, Heike E.
通讯作者：
Daldrup-Link, Heike E.
影响因子：
37.8
作者：
Hill, JM;Dick, AJ;Lederman, RJ
通讯作者：
Lederman, RJ
影响因子：
3.8
作者：
Chen, Ying-Chun;Hsiao, Jong-Kai;Huang, Dong-Ming
通讯作者：
Huang, Dong-Ming