In vivo tracking of transplanted mononuclear cells using manganese-enhanced magnetic resonance imaging (MEMRI).
In vivo tracking of transplanted mononuclear cells using manganese-enhanced magnetic resonance imaging (MEMRI).
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DOI：
10.1371/journal.pone.0025487
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Saga T
中科院分区：
文献类型：
--
作者：
Odaka K;Aoki I;Moriya J;Tateno K;Tadokoro H;Kershaw J;Minamino T;Irie T;Fukumura T;Komuro I;Saga T
单核细胞（MNCs）的移植先前已被测试作为一种方法，以诱导治疗性血管生成治疗肢体缺血的临床试验。需要非侵入性高分辨率成像来跟踪细胞并评估细胞移植后的临床相关性。在缺血大鼠腿部研究了MRI可以提供锰造影剂标记的MNCs的体内检测和长期观察的假设。使用7特斯拉高场磁共振成像（MRI）评价Mn标记的MNC。肌内移植的锰标记的MNCs在移植到缺血腿后至少7天和21天内用MRI可视化。Mn标记的MNCs的分布与单光子发射计算机断层扫描（SPECT）和荧光显微镜下DiI染色的MNCs测量的111 In标记的MNCs的分布相似。此外，在移植后1-2天，注射完整Mn标记的MNC的部位的体积显著大于注射死亡MNC的部位，尽管在缺血腿中也发现死亡Mn标记的MNC约2周。在43天时，在完整Mn-MNC植入部位中由CD 31阳性细胞（作为毛细血管内皮细胞的标记物）覆盖的面积显著大于植入死亡Mn-MNC的部位。目前的Mn增强MRI方法能够以150-175 µm的平面内空间分辨率可视化移植区域，并允许在同一受试者中长时间观察标记的MNC的迁移。在进一步优化后，基于MRI的Mn增强细胞追踪可能是一种有用的技术，用于评估细胞治疗的研究和临床应用。
Transplantation of mononuclear cells (MNCs) has previously been tested as a method to induce therapeutic angiogenesis to treat limb ischemia in clinical trials. Non-invasive high resolution imaging is required to track the cells and evaluate clinical relevance after cell transplantation. The hypothesis that MRI can provide in vivo detection and long-term observation of MNCs labeled with manganese contrast-agent was investigated in ischemic rat legs. The Mn-labeled MNCs were evaluated using 7-tesla high-field magnetic resonance imaging (MRI). Intramuscular transplanted Mn-labeled MNCs were visualized with MRI for at least 7 and up to 21 days after transplantation in the ischemic leg. The distribution of Mn-labeled MNCs was similar to that of 111In-labeled MNCs measured with single-photon emission computed tomography (SPECT) and DiI-dyed MNCs with fluorescence microscopy. In addition, at 1–2 days after transplantation the volume of the site injected with intact Mn-labeled MNCs was significantly larger than that injected with dead MNCs, although the dead Mn-labeled MNCs were also found for approximately 2 weeks in the ischemic legs. The area covered by CD31-positive cells (as a marker of capillary endothelial cells) in the intact Mn-MNCs implanted site at 43 days was significantly larger than that at a site implanted with dead Mn-MNCs. The present Mn-enhanced MRI method enabled visualization of the transplanted area with a 150–175 µm in-plane spatial resolution and allowed the migration of labeled-MNCs to be observed for long periods in the same subject. After further optimization, MRI-based Mn-enhanced cell-tracking could be a useful technique for evaluation of cell therapy both in research and clinical applications.