IGF-1对人源脐带间充质细胞神经分化影响的研究

发布时间：2018-05-14 19:22

本文选题：人源脐带间充质干细胞 + 胰岛素样生长因子-1　；参考：《暨南大学》2017年博士论文

【摘要】：目的:研究人员目前已经证实了人源脐带间充质干细胞(UC-MSCs)具有治疗多种疾病的潜力。近年来,研究人员成功地将该细胞分化为神经前体细胞(NPCs),为神经疾病的治疗提供了一种新的细胞来源。但是,在以后的临床研究中,UC-MSCs向NPCs分化的方法仍需要进一步改进和完善。本研究旨在利用胰岛素样生长因子-1(IGF-1),优化人源脐带间充质干细胞的神经分化效率,为UC-MSCs在神经系统疾病的临床治疗开发新的研究途径。方法:通过逆转录病毒感染的方法建立胰岛素样生长因子-1(IGF-1)过度表达人源脐带间充质干细胞(UC-MSCs-IGF)模型,进而通过神经诱导分化为神经前体细胞。用RNA芯片,qPCR和western-blot分别检测人源脐带间充质干细胞来源的神经前体细胞的增殖和分化能力,以及相关通路机制。结果:与常规人源脐带间充质干细胞相比较,胰岛素生长因子-1过表达的人源脐带间充质干细胞(UC-MSCs-IGF-1)分化而来的神经前体细胞具有更强的增殖能力和更多的Pax6阳性以及Nestin阳性细胞。另外,UC-MSCs-IGF-1分化而来的神经前体细胞在体外实验中终末分化时可更高效率地分化为星形胶质细胞。RNA芯片分析表明一些与神经分化和神经前体细胞增殖能力相关的基因在UC-MSCs-IGF-1中明显上调,并且该结论在qPCR和western-blot得到证实。最终,用IGF-1-siRNA转染UC-MSCs-IGF-1,转染后UC-MSCs-IGF-1衍生的神经前体细胞增值能力和星形胶质细胞分化能力减弱。结论:此研究表明胰岛素样生长因子-1可以提高人源脐带间充质干细胞的神经分化能力,并且为增强人源脐带间充质干细胞衍生的神经前体细胞向星形胶质细胞分化提供了一项独特的方法。
[Abstract]:Objective: human umbilical cord mesenchymal stem cells (UC-MSCs) have been demonstrated to have potential in the treatment of many diseases. In recent years, researchers have successfully differentiated the cells into neural precursor cells (NPCs), which provides a new source of cells for the treatment of neurological diseases. However, the differentiation of UC-MSCs into NPCs still needs to be further improved and improved in future clinical studies. The purpose of this study was to optimize the neural differentiation efficiency of human umbilical cord mesenchymal stem cells by using insulin-like growth factor-1 (IGF-1), and to develop a new approach for the clinical treatment of UC-MSCs in nervous system diseases. Methods: the UC-MSCs-IGF model of overexpression of human umbilical cord mesenchymal stem cells (UC-MSCs-IGF) was established by retrovirus infection and then differentiated into neural precursor cells. The proliferation and differentiation of neural progenitor cells derived from human umbilical cord mesenchymal stem cells were detected by RNA microarray qPCR and western-blot. Results: compared with normal human umbilical cord mesenchymal stem cells, UC-MSCs-IGF-1 derived human umbilical cord mesenchymal stem cells (UC-MSCs-IGF-1) derived from the overexpression of insulin growth factor 1 (IGF-1) have stronger proliferative ability, more Pax6 positive cells and more Nestin positive cells. In addition, UC-MSCs-IGF-1 differentiated neural progenitor cells could differentiate into astrocytes. RNA chip analysis showed that some genes related to neural differentiation and neural precursor cell proliferation were more efficiently differentiated during terminal differentiation in vitro. In UC-MSCs-IGF-1, it was significantly up-regulated, This conclusion is confirmed by qPCR and western-blot. Finally, after transfection of UC-MSCs-IGF-1 with IGF-1-siRNA, the proliferation and astrocyte differentiation ability of neural precursor cells derived from UC-MSCs-IGF-1 were decreased. Conclusion: this study suggests that insulin-like growth factor-1 can enhance the neural differentiation of human umbilical cord mesenchymal stem cells. It also provides a unique method for enhancing the differentiation of neural precursor cells derived from human umbilical cord mesenchymal stem cells into astrocytes.
【学位授予单位】：暨南大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R741

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