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Therapeutic benefit of TH-engineered mesenchymal stem cells for Parkinson's disease.

机译:TH改造的间充质干细胞对帕金森氏病的治疗益处。

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The present study was designed to assess the potential of marrow stromal cells (MSCs) to deliver therapeutic genes to the brain and result in biologically significant functional recovery. The tyrosine hydroxylase (TH) gene was transfected to MSCs with an adeno-associated virus (AAV) vector. MSCs expressing TH gene were transplanted into the striatum of Parkinson's disease (PD) rat. The asymmetric rotation of these models after apomorphine administration was detected every week after transplantation. Six weeks after grafting, animals were sacrificed. Some brains were sectioned to do TH immunohistochemistry. The others were used to detect the dopamine levels by high-performance liquid chromatograph and electrochemical detection (HPLC-ECD). The results showed that MSCs multiply rapidly and formed fibroblast colony-forming units in primary culture. The gene expression efficiency was about 75%. The rounds of asymmetric rotation after apomorphine administration decreased after TH-engineered MSCs were grafted. Histological examination showed that TH gene was expressed around the transplantation points. The dopamine level in the lesioned striatum of rats injected with TH-MSCs was significantly greater than that in rats treated with LacZ-MSCs (P < 0.05). All the data demonstrated that MSCs could readily be genetically engineered. Therefore, MSCs could be useful gene delivery vehicles of gene therapy for Parkinson's disease.
机译:本研究旨在评估骨髓基质细胞(MSC)将治疗性基因传递到大脑并导致生物学上重要的功能恢复的潜力。用腺相关病毒(AAV)载体将酪氨酸羟化酶(TH)基因转染至MSC。将表达TH基因的MSC移植到帕金森氏病(PD)大鼠的纹状体中。移植后每周检查一次阿扑吗啡给药后这些模型的不对称旋转。移植六周后,处死动物。将一些脑切开以进行TH免疫组织化学。其他通过高效液相色谱和电化学检测(HPLC-ECD)来检测多巴胺水平。结果表明,MSCs在原代培养中迅速繁殖并形成成纤维细胞集落形成单位。基因表达效率约为75%。在TH工程化的MSCs移植后,阿扑吗啡给药后的不对称旋转次数减少。组织学检查显示TH基因在移植点周围表达。注射TH-MSC的大鼠病变纹状体中的多巴胺水平显着高于使用LacZ-MSC的大鼠(P <0.05)。所有数据表明,MSC可以很容易地进行基因工程改造。因此,MSCs可能是帕金森氏病基因治疗的有用基因传递载体。

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