Math5在骨髓间充质干细胞向视网膜神经节样细胞分化过程中作用

发布时间：2018-05-26 00:26

  本文选题：Math5 + 骨髓间充质干细胞　； 参考：《吉林大学》2010年博士论文

【摘要】： 骨髓间充质干细胞(bone marrow mesenchymal stem cells BMSCs)具有向视网膜神经节样细胞分化的能力,但现诱导条件下其分化率较低,通过外源性给予促进神经分化关键基因来提高BMSCs的分化效率,将是一个切实可行的方案。Math5目前被认为是鼠视网膜神经节细胞生成的关键基因,将Math5导入BMSCs,若能够促进其分化,将为有效解决BMSCs的低神经分化问题提供一新的思路。 本研究采用不同方法体外诱导BMSCs分化,进一步证明其向视网膜神经节样细胞定向分化潜能。化学合成Math5并成功构建同源重组腺病毒载体,对BMSCs进行转染。转染后细胞稳定表达Math5,可分化为视网膜神经节样细胞,并且在视网膜条件分化液诱导环境下该分化能力得到一定程度的提高。这一分化过程中RT-PCR检测显示GAP-43和Brn-3b表达上调。 上述实验证明BMSCs具有向视网膜神经节样细胞定向分化的能力；成功构建的Math5腺病毒载体可高效转染BMSCs并被表达；Math5能够促使BMSCs向视网膜神经节样细胞分化,在视网膜条件分化液诱导下该作用更明确；Math5发挥作用推测与激活下游GAP-43、Brn-3b有关。该研究结果为解决BMSCs的低分化率问题提供了新的研究方向,并初步揭示了Math5发挥作用的机制,为其后续应用奠定理论基础。
[Abstract]:Bone mesenchymal stem cells (marrow mesenchymal stem cells BMSCs) have the ability to differentiate into retinal ganglion like cells (RGCs), but the differentiation rate is relatively low under the present induction condition. The differentiation efficiency of BMSCs can be improved by exogenous giving key genes to promote neural differentiation. Math5 is considered to be a key gene in the formation of rat retinal ganglion cells. The introduction of Math5 into BMSCs, if it can promote its differentiation, will provide a new way to effectively solve the problem of low nerve differentiation of BMSCs. In this study, different methods were used to induce the differentiation of BMSCs into retinal ganglion like cells (RGCs) in vitro. Math5 was chemically synthesized and the homologous recombinant adenovirus vector was successfully constructed, and BMSCs was transfected. After transfection, the cells expressed Math5 stably, which could differentiate into retinal gangliona-like cells, and the differentiation ability was improved to some extent under the condition of retinal conditioned differentiation fluid. The expression of GAP-43 and Brn-3b was up-regulated by RT-PCR during this differentiation. The results show that BMSCs has the ability to differentiate into retinal ganglion like cells, and that the successfully constructed adenovirus vector of Math5 can efficiently transfect BMSCs and be expressed to induce BMSCs to differentiate into retinal gangliona-like cells. The role of Math5 may be related to the activation of GAP-43 Brn-3b downstream under the induction of retinal conditioned differentiation fluid. The results of this study provide a new research direction for solving the problem of low differentiation rate of BMSCs, and preliminarily reveal the mechanism of the role of Math5, and lay a theoretical foundation for its subsequent application.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2010
【分类号】：R329

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