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在大鼠模型中使用GDNF过表达的骨髓干细胞改善脊髓损伤的干细胞治疗

Improved stem cell therapy of spinal cord injury using GDNF-overexpressed bone marrow stem cells in a rat model.

作者信息

Shahrezaie Mostafa, Mansour Reyhaneh Nassiri, Nazari Bahare, Hassannia Hadi, Hosseini Fatemeh, Mahboudi Hossein, Eftekhary Mohamad, Kehtari Mousa, Veshkini Arash, Ahmadi Vasmehjani Abbas, Enderami Seyed Ehsan

机构信息

Department of Orthopedic Surgery and Research, AJA University of Medical Science, Iran.

Department of Stem Cells Biology, Stem Cell Technology Research Center, Tehran, Iran.

出版信息

Biologicals. 2017 Nov;50:73-80. doi: 10.1016/j.biologicals.2017.08.009. Epub 2017 Aug 26.

Abstract

The use of stem cell base therapy as an effective strategy for the treatment of spinal cord injury (SCI) is very promising. Although some strategy has been made to generate neural-like cells using bone marrow mesenchymal stem cells (BMSCs), the differentiation strategies are still inefficiently. For this purpose, we improved the therapeutic outcome with utilize both of N-neurotrophic factor derived Gelial cells (GDNF) gene and differentiation medium that induce the BMSCs into the neural-like cells. The differentiated GDNF overexpressed BMSCs (BMSCs-GDNF) were injected on the third day of post-SCI. BBB score test was performed for four weeks. Two weeks before the end of BBB, biotin dextranamin was injected intracrebrally and at the end of the fourth week, the tissue was stained. BBB scores were significantly different in BMSCs-GDNF injected and control animals. Significant difference in axon counting was observed in BMSCs-GDNF treated animals compared to the control group. According to the results, differentiated BMSCs-GDNF showed better results in comparison to the BMSCs without genetic modification. This study provides a new strategy to investigate the role of simultaneous in stem cell and gene therapy for future neural-like cells transplantation base therapies for SCI.

摘要

使用基于干细胞的疗法作为治疗脊髓损伤(SCI)的有效策略非常有前景。尽管已经制定了一些策略来利用骨髓间充质干细胞(BMSCs)生成神经样细胞,但分化策略仍然效率低下。为此,我们通过利用N-神经营养因子衍生的胶质细胞源性神经营养因子(GDNF)基因和诱导BMSCs分化为神经样细胞的分化培养基来改善治疗效果。在脊髓损伤后的第三天注射分化的GDNF过表达骨髓间充质干细胞(BMSCs-GDNF)。进行四周的BBB评分测试。在BBB测试结束前两周,脑内注射生物素葡聚糖胺,并在第四周结束时对组织进行染色。注射BMSCs-GDNF的动物和对照动物的BBB评分有显著差异。与对照组相比,在接受BMSCs-GDNF治疗的动物中观察到轴突计数有显著差异。根据结果,与未进行基因修饰的BMSCs相比,分化的BMSCs-GDNF显示出更好的效果。本研究为未来基于干细胞和基因疗法的神经样细胞移植治疗脊髓损伤的同时作用研究提供了一种新策略。

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