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首页> 外文期刊>The Journal of Nuclear Medicine >A Novel Cell-Based Therapy for Contusion Spinal Cord Injury Using GDNF-Delivering NIH3T3 Cells with Dual Reporter Genes Monitored by Molecular Imaging.
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A Novel Cell-Based Therapy for Contusion Spinal Cord Injury Using GDNF-Delivering NIH3T3 Cells with Dual Reporter Genes Monitored by Molecular Imaging.

机译：一种新颖的基于细胞的挫伤性脊髓损伤治疗方法，该方法采用GDNF传递的NIH3T3细胞和分子成像监测的双重报告基因进行。

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This aim of our study was to evaluate a novel cell-based therapy for contusion spinal cord injury (SCI) using embryonic-derived NIH3T3 cells, which endogenously express glial cell line-derived neurotrophic factor (GDNF). METHODS: Proliferation and differentiation of transplanted NIH3T3 cells and their anti-apoptotic effects were examined after their engraftment into the spinal cords of Long-Evans rats subjected to acute SCI at the T10 vertebral level by a New York University impactor device. NIH3T3 cells were initially engineered to contain dual reporter genes, namely thymidine kinase (T) and enhanced green fluorescence protein (G), for in vivo cell tracking by both nuclear and fluorescence imaging modalities. RESULTS: Planar and fluorescence imaging demonstrated that transplanted NIH3T3-TG cells at the L1 vertebral level migrated 2 cm distal to the injury site as early as 2 h, and the signals persisted for 48 h after SCI. The expression of GDNF by NIH3T3-TG cells was then confirmed by immunohistochemical analysis both in vitro and in vivo. GDNF-secreting NIH3T3-TG transplant provided anti-apoptotic effects in the injured cord over the period of 3 wk. Finally, NIH3T3-TG cells cultured under neuronal differentiation medium exhibited both morphologic and genetic resemblance to neuronal cells. CONCLUSION: GDNF-secreting NIH3T3-TG cells in combination with molecular imaging could be a platform for developing therapeutic tools for acute SCI.
机译：我们研究的目的是评估使用胚胎来源的NIH3T3细胞（基于内源性表达神经胶质细胞系神经营养因子（GDNF））的挫伤性脊髓损伤（SCI）的新型细胞疗法。方法：采用纽约大学冲击器，检测移植的NIH3T3细胞在T10椎骨水平下植入急性SCI的Long-Evans大鼠脊髓后的增殖和分化及其抗凋亡作用。 NIH3T3细胞最初经过工程改造，以包含双重报告基因，即胸苷激酶（T）和增强的绿色荧光蛋白（G），用于通过核和荧光成像方式进行体内细胞跟踪。结果：平面和荧光成像显示，在L1椎骨水平移植的NIH3T3-TG细胞最早于2 h移至损伤部位远端2 cm，信号在SCI后持续48 h。然后通过免疫组织化学分析在体外和体内证实了NIH3T3-TG细胞GDNF的表达。分泌GDNF的NIH3T3-TG移植物在3周内对受伤的脐带提供了抗凋亡作用。最后，在神经元分化培养基下培养的NIH3T3-TG细胞与神经元细胞在形态和遗传上都相似。结论：分泌GDNF的NIH3T3-TG细胞与分子成像相结合可能是开发急性SCI治疗工具的平台。

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