脑脊液内移植小鼠骨髓基质细胞对铜锌超氧化物歧化酶1转基因小鼠的作用

摘要

目的 研究脑脊液内移植小鼠骨髓基质细胞(mouse marrow stromal cells,mMSCs)对铜锌超氧化物歧化酶1 (Cu/Zn superoxide dismutase 1,SOD1)转基因小鼠的作用.方法 将5×105个mMSCs经枕大池单次移植(8周龄时)或多次移植(8、10和12周龄时)到SOD1转基因小鼠的脑脊液中.通过临床观察、体重、悬线实验和运动神经元计数来评估小鼠的疾病进展.结果 单次移植mMSCs对SOD1转基因小鼠没有明显有益的作用；与对照组SOD1转基因小鼠相比,多次移植mMSCs则能够减轻体重的丢失,改善运动行为,保护运动神经元,更重要的是还能够将SOD1小鼠的存活时间延长17 d[(157±15)d与(140±11)d；x2=7.56,P＜0.01].结论 我们认为鞘内移植可能是一种有前景的细胞移植途径,且多次移植mMSCs对于SOD1小鼠的治疗作用是十分必要的.%Objective To investigate the effect of transplantation of mouse marrow stromal cells (mMSCs) on Cu/Zn superoxide dismutase 1 (SOD1) transgenic mice through cerebrospinal fluid (CSF) injection.Methods We delivered 5 × 105 mMSCs into SOD1 transgenic mice by single injection to CSF at the age of 8 weeks or by multiple injections at the age of 8,10 and 12 weeks.Neurologic phenotype observation,weight measurement,hanging wire test and motor neuron counts were used to assess disease progression of SOD1 mice.Results Single transplantation of mMSCs didn' t show beneficial effect on SOD1 mice.Compared with vehicle-treated mice,SOD1 transgenic mice with multiple transplantations of mMSCs demonstrated attenuated weight loss,improved motor performance,decreased motor neuron loss,and importantly,prolonged survival by 17 days ((157 ± 15) d vs (140 ± 11) d; x2 =7.56,P ＜ 0.01).Conclusion Intrathecal injection could be an effective route of cell transplantation,and multiple transplantations of mMSCs are needed to achieve the therapeutic effect on SOD1 mice.