骨髓间充质干细胞移植对颅脑损伤大鼠神经功能的影响

Effects of bone mesenchymal marrow stem cells on neurological function of rats with traumatic brain injury

目的研究骨髓间充质干细胞(BMSCs)移植对颅脑损伤大鼠神经功能的影响。方法分离、纯化大鼠BMSCs,并用左旋多聚赖氨酸-超顺磁性纳米铁颗粒(PLL-SPIO)复合物对BMSCs进行标记。采用改良Feeney法制成创伤性颅脑损伤大鼠模型60只,随机均分为两组。实验组在脑损伤部位的对侧立体定向移植PLL-SPIO标记的BMSCs;对照组注入等量的生理盐水。在移植后第1、3、7、14和28天时采用改良神经功能损伤严重程度评分(mNSS)对各组大鼠进行评分;然后行MRI扫描,观察脑实质内的信号变化及BMSCs在脑内的迁移情况。应用组织学检查,观察脑损伤部位的病理变化。结果含量为25μg Fe/ml的PLL-SPIO培养液能成功标记BMSCs(标记率为100%)。实验组大鼠在细胞移植后的第3、7、14天时mNSS低于对照组(P<0.05);移植后第7天,BMSCs从植入部位沿胼胝体向脑损伤区域迁移并分布于损伤区域。结论脑内立体定向移植BMSCs能明显促进创伤性颅脑损伤大鼠神经功能的恢复。

Objective To explore the effects of bone mesenchymal marrow stem cells（BMSCs） on neurological function of rats with traumatic brain injury（TBI）. Methods The BMSCs were isolated and purified from rat bone marrow,which were then labeled with a complex of poly-lysine（PLL） and SPIO. The TBI model was established by free-falling instrument of Feeney in 60 male SD rats, which then were randomly divieded into two groups. The PLL-SPIO-labeled BMSCs were stereotactically transplanted into the brain opposite to the TBI side in group A. The same volume of normal saline instead of BMSCs was injected in group B as the control. The evaluation with modified Neurological Severity Score（mNSS） was performed on the 1^st, 3^rd, 7^th, 14^th and 28^th day after TBI. The signal changes in the brain and the distribution and migration of SPIO-labeled BMSCs were observed by MRI. Pathological changes were ohserved in the injuried part of the brain by HE dyeing and Prussian blue staining. Results The PLL-SPIO 25μgFe/ml culture solution successfully labeled BMSCs with a success rate of 100%. The mNSS scores were significantly lower in group A than those in group B on the 3^rd, 7^th and 14^th day after TBI（P〈0. 05）. The SPIO-labeled BMCSs were detected to migrate and distribute from the transplanted area to the injuried part of the brain along with the corpus callosum. Conclusion Direct stereotactic transplantation of BMSCs could improve the neurological fanction of rats with TBI.