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脑梗死大鼠脑内移植超顺磁性氧化铁颗粒标记神经干细胞后的MR示踪研究 被引量:20

Magnetic resonance tracking of transplanted neural stem cells labeled with superparamagnetic iron oxide nanoparticles in ischemic rat
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摘要 目的探讨超顺磁性氧化铁颗粒(SPIO)标记的胎鼠神经干细胞(NSCs)在脑梗死模型大鼠脑内移植后,MR示踪观察的可行性。方法大鼠脑梗死模型24只,按随机数字表法分为3组第1组大鼠同侧尾状核移植SPIO和5-溴脱氧尿核苷(BrdU)双标记的NSCs;第2组对侧尾状核移植双标记的NSCs;第3组对侧尾状核移植未标记的NSCs。移植后1、3、5、7周后进行MR示踪观察,选择T2WI和梯度回波(GRE)序列,成像后相应时间点每组处死2只大鼠,取脑组织冰冻切片后进行普鲁士蓝染色及BrdU染色。结果移植后1周MRI显示移植标记细胞组在注射点处可见类圆形低信号影,未标记细胞组注射点未见异常信号影;3周后,第1组梗死皮层下可见线状低信号影;移植5周后,第2组沿胼胝体走行可见扇形低信号影,尖端指向病灶。GRE序列显示标记细胞较清晰,而T2WI显示梗死病灶和大鼠脑正常结构较清晰。相应时间点相应部位普鲁士蓝染色及BrdU染色可见阳性细胞,与MRI结果相符。结论超顺磁性氧化铁颗粒和BrdU双标记的神经干细胞移植至大鼠脑内后可迁移到病灶区;MR成像能够在活体内连续示踪观察神经干细胞的迁移及分布情况。 Objective To explore the methods of labeling neural stem cells (NSCs) with superparamagnetic iron oxide (SPIO) particles, and to monitor the labeled cells after transplantation into the ischemic rat with MR scanning. Methods Neural stem cells were derived from the brain of embryonic 14- day rat and co-labeled with SPIO mediated by poly-L-lysine and bromodeoxyuridine ( BrdU ). The 24 focal cortical infarction models of male Sprague-Dawley rats were induced ten days before transplantation. The models were divided into three groups in random : ( 1 ) The labeled NSCs were transplanted into the ipsilateral caudate nucleus; (2) The labeled NSCs were transplanted into the contralateral caudate nucleus; (3) The unlabeled NSCs were transplanted into the contralateral caudate nucleus. MR scanning was performed to monitor the transplanted cells after 1,3,5,7 weeks. After MR imaging, two rats of each group were killed and performed Prussian blue staining and BrdU staining of the histological sections. Results During the first postimplantation, MR scanning showed well-defined hyperintensity in the cortical infarct lesion. The implanted labeled cells were visible on MR images as a hypointense area at the injection site (caudate nucleus) in the first and the second group. In group 3, the unlabeled cells were not observed. Three weeks later, linear hypointensity was observed in the subcortical infarct lesion in group 1. After five weeks, the low signal intensity could be seen in the corpus callosum and formed a triangle-like troop with its tip directed to the lesion side in group 2. Seven weeks later, hypointensity was observed in the lesion of the second group. GRE sequence was more clearly than T2 weight imaging in showing labeled cells. MR scanning results were confirmed by Prussian blue staining and BrdU staining of histological sections. Conclusion NSCs colabeled with SPIO nanoparticles and BrdU could migrate into the lesions after transplanted into rats' brains. MR scanning is useful and noninvasive to tracking the location and distribution of the labeled neural stem cells.
出处 《中华放射学杂志》 CAS CSCD 北大核心 2006年第2期122-126,共5页 Chinese Journal of Radiology
基金 北京市自然科学基金资助项目(7062013) 北京市自然科学基金资助项目(7032009) 国家自然科学基金资助项目(30370427) 国家"十五"科技攻关项目(2004BA714B06-02)
关键词 超顺磁性氧化铁 磁共振成像 干细胞 脑梗塞 大鼠 Superparamagnetic iron oxide Magnetic resonance imaging Stem cells Brain infarction Rats
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参考文献15

  • 1Daldrup-Link HE,Rudelius M,Oostendorp RA,et al.Targeting of hematopoietic progenitor cells with MR contrast agents.Radiology,2003,228:760-767.
  • 2Arbab AS,Bashaw LA,Miller BR,et al.Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging.Radiology,2003,229:838-846.
  • 3Frank JA,Miller BR,Arbab AS,et al.Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents.Radiology,2003,228:480-487.
  • 4Arbab AS,Bashaw LA,Miller BR,et al.Intracytoplasmic tagging of cells with ferumoxides and transfection agent for cellular magnetic resonance imaging after cell transplantation:methods and techniques.Transplantation,2003,76:1123-1130.
  • 5Arbab AS,Yocum GT,Kalish H,et al.Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI.Blood,2004,104:1217-1223.
  • 6Hoehn M,Kustermann E,Blunk J,et al.Monitoring of implanted stem cell migration in vivo:a highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat.Proc Natl Acad Sci U S A,2002,99:16267-16272.
  • 7Zhang ZG,Jiang Q,Zhang R,et al.Magnetic resonance imaging and neurosphere therapy of stroke in rat.Ann Neurol,2003,53:259-263.
  • 8Jendelova P,Herynek V,Urdzikova L,et al.Magnetic resonance tracking of transplanted bone marrow and embryonic stem cells labeled by iron oxide nanoparticles in rat brain and spinal cord.J Neurosci Res,2004,76:232-243.
  • 9Jendelova P,Herynek V,DeCroos J,et al.Imaging the fate of implanted bone marrow stromal cells labeled with superparamagnetic nanoparticles.Magn Reson Med,2003,50:767-776.
  • 10Bulte JW,Ben-Hur T,Miller BR,et al.MR microscopy of magnetically labeled neurospheres transplanted into the Lewis EAE rat brain.Magn Reson Med,2003,50:201-205.

二级参考文献59

  • 1Weissleder R. Molecular imaging: exploring the next frontier.Radiology, 1999, 212: 609-614.
  • 2Unger EC. How can superparamagnetic iron oxides be used to monitor disease and treatment? Radiology, 2003, 229: 615-616.
  • 3Bicknese AR, Goodwin HS, Quinn CO, et al. Human umbilical cord blood cells can be induced to express markers for neurons and glia. Cell Transplant, 2002, 11:261-264.
  • 4Deans R J, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol, 2000, 28: 875-884.
  • 5Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol, 2000, 109 : 235-242.
  • 6Yeh TC, Zhang W, Ildstad ST, et al. In vivo dynamic MRI tracking of rat T-cells labeled with superparamagnetic iron-oxide particles.Magn Reson Med, 1995, 33:200-208.
  • 7Josephson L, Tung CH, Moore A, et al. High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide coniuzates. Bioconiuz Chem, 1999, 10: 186-191.
  • 8Daldrup-Link HE, Rudelius M, Oostendorp RA, et al. Targeting of hematopoietic progenitor cells with MR contrast agents. Radiology,2003, 228: 760-767.
  • 9Weissleder R, Stark DD, Engelstad BL, et al. Superparamagetic iron oxide: pharmacokinetics and toxicity. AJR, 1989,152: 167-173.
  • 10Lee IH, Bulte JW, Schweinhardt P, et al. In vivo magnetic resonance tracking of olfactory ensheathing glia grafted into the rat spinal cord. Exp Neurol, 2004, 187: 509-516.

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