Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells

Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells
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DOI:
10.1161/01.cir.0000084537.66419.7a
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发表时间:
2003-08-26
期刊:
影响因子:
37.8
通讯作者:
Lederman, RJ
Lederman, RJ
中科院分区:
医学1区
文献类型:
--
作者:
Hill, JM;Dick, AJ;Lederman, RJ

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背景 - 心内膜心肌干细胞的输送和追踪由于无法在跳动的心脏中对移植细胞进行无创成像而受到限制。我们假设间充质干细胞 (MSC) 可以用铁荧光团颗粒 (IFP) 标记,以提供体内 MRI 对比,以评估即时和长期定位。方法和结果 - 从猪中分离 MSC。 MSC 与 IFP 的短期孵育可产生剂量依赖性且有效的标记。标记的细胞在多次传代中仍保持活力,并保留体外增殖和分化能力。将标记的MSC(10(4)至10(6)细胞/150μL)经皮注射到猪的正常和新梗死的心肌中。 1、3 和 1 只动物分别接受了 4、8 和 21 天的连续心脏 MRI (1.5T)。对琼脂中包埋的细胞进行体内和体外 MRI 对比特性测量。可以检测到含有少至 10(5) 个 MSC 的注射部位,并且在组织学上含有完整的带有 IFP 的 MSC。结论 - MSC 的 IFP 标记提供了有用的 MRI 对比度,使得在移植到正常和梗塞心肌后,可以在传统心脏 MR 扫描仪上轻松检测跳动的心脏。双标记的 MSC 可以在与注射部位相对应的位置进行识别,既可以使用荧光显微镜在体外进行识别,也可以使用 MRI 上的磁敏对比在体内进行识别。该技术可以实现干细胞保留、植入和迁移的有效体内研究。
Background - Delivery and tracking of endomyocardial stem cells are limited by the inability to image transplanted cells noninvasively in the beating heart. We hypothesized that mesenchymal stem cells (MSCs) could be labeled with a iron fluorophore particle (IFP) to provide MRI contrast in vivo to assess immediate and long-term localization.Methods and Results - MSCs were isolated from swine. Short-term incubation of MSCs with IFP resulted in dose-dependent and efficient labeling. Labeled cells remained viable for multiple passages and retained in vitro proliferation and differentiation capacity. Labeled MSCs (10(4) to 10(6) cells/150 muL) were injected percutaneously into normal and freshly infarcted myocardium in swine. One, 3, and 1 animals underwent serial cardiac MRI ( 1.5T) for 4, 8, and 21 days, respectively. MRI contrast properties were measured both in vivo and in vitro for cells embedded in agar. Injection sites containing as few as 10(5) MSCs could be detected and contained intact IFP-bearing MSCs on histology.Conclusions - IFP labeling of MSCs imparts useful MRI contrast, enabling ready detection in the beating heart on a conventional cardiac MR scanner after transplantation into normal and infarcted myocardium. The dual-labeled MSCs can be identified at locations corresponding to injection sites, both ex vivo using fluorescence microscopy and in vivo using susceptibility contrast on MRI. This technology may permit effective in vivo study of stem cell retention, engraftment, and migration.