Near-Infrared Fluorescence Labeling Allows Noninvasive Tracking of Bone Marrow Stromal Cells Transplanted Into Rat Infarct Brain
Near-Infrared Fluorescence Labeling Allows Noninvasive Tracking of Bone Marrow Stromal Cells Transplanted Into Rat Infarct Brain
复制标题
DOI：
10.1227/neu.0b013e318208f891
复制
发表时间：
2011-04
期刊：
影响因子：
4.8
通讯作者：
T. Sugiyama;S. Kuroda;T. Osanai;H. Shichinohe;Y. Kuge;Masaki Ito;M. Kawabori;Y. Iwasaki
中科院分区：
文献类型：
--
作者：
T. Sugiyama;S. Kuroda;T. Osanai;H. Shichinohe;Y. Kuge;Masaki Ito;M. Kawabori;Y. Iwasaki
背景：需要非侵入性成像技术来验证细胞移植疗法对中枢神经系统疾病的治疗效果。目的：评估近红外（NIR）发射荧光示踪剂量子点是否有助于无创地观察移植到活体动物梗死脑中的骨髓基质细胞（BMSC）。方法：用QD800标记大鼠BMSC。精确优化近红外荧光可视化的体外和体内条件。在损伤后7天，将QD800标记的BMSC立体定向移植到遭受永久性大脑中动脉闭塞的大鼠的同侧纹状体中。使用近红外荧光成像技术，在移植后 8 周内连续观察 BMSC 的行为。结果：近红外荧光成像可在移植后8周内无创地检测通过头皮植入梗死周围新皮质的移植骨髓间充质干细胞发出的近红外荧光。强度逐渐增加，并在4周时达到顶峰。离体近红外荧光成像和组织学分析的结果支持了该结果。结论：近红外荧光成像对于监测啮齿类动物大脑中供体细胞的行为具有重要价值。这些结果将为开发无创近红外荧光成像作为追踪移植到大脑中的骨髓间充质干细胞的方式提供新的机会。
BACKGROUND:Noninvasive imaging techniques would be needed to validate the therapeutic benefits of cell transplantation therapy for central nervous system disorders. OBJECTIVE:To evaluate whether near-infrared (NIR)-emitting fluorescence tracer, quantum dots, would be useful to noninvasively visualize the bone marrow stromal cells (BMSC) transplanted into the infarct brain in living animals. METHODS:Rat BMSCs were labeled with QD800. In vitro and in vivo conditions to visualize NIR fluorescence were precisely optimized. The QD800-labeled BMSCs were stereotactically transplanted into the ipsilateral striatum of the rats subjected to permanent middle cerebral artery occlusion 7 days after the insult. Using the NIR fluorescence imaging technique, the behaviors of BMSCs were serially visualized during the 8 weeks after transplantation. RESULTS:NIR fluorescence imaging could noninvasively detect the NIR fluorescence emitted from the transplanted BMSCs engrafted in the peri-infarct neocortex through the scalp up to 8 weeks after transplantation. The intensity gradually increased and reached the peak at 4 weeks. The results were supported by the findings on ex vivo NIR fluorescence imaging and histological analysis. CONCLUSION:NIR fluorescence imaging is valuable in monitoring the behaviors of donor cells in the rodent brain. The results would allow new opportunities to develop noninvasive NIR fluorescence imaging as a modality to track the BMSCs transplanted into the brain.