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Exploiting the impact of the secretome of MSCs isolated from different tissue sources on neuronal differentiation and axonal growth
Biochimie ( IF 3.3 ) Pub Date : 2018-08-02 , DOI: 10.1016/j.biochi.2018.07.026
Rita Catarina Assunção-Silva , Bárbara Mendes-Pinheiro , Patrícia Patrício , Leo A. Behie , Fábio Gabriel Teixeira , Luísa Pinto , António José Salgado

Cell transplantation using Mesenchymal stem cell (MSC) secretome have recently been presented as a possible free-based therapy for CNS related disorders. MSC secretome is rich in several bio-factors that act synergically towards the repair of damaged tissues, thus making it an ideal candidate for regenerative applications. Great effort is currently being made to map the molecules that compose the MSC secretome. Previous proteomic characterization of the secretome (in the form of conditioned media - CM) of MSCs derived from adipose tissue (ASC), bone-marrow (BMSC) and umbilical cord (HUCPVC) was performed by our group, where proteins relevant for neuroprotection, neurogenic, neurodifferentiation, axon guidance and growth functions were identified. Moreover, we have found significant differences among the expression of several molecules, which may indicate that their therapeutic outcome might be distinct. Having this in mind, in the present study, the neuroregulatory potential of ASC, BMSC and HUCPVC CM in promoting neurodifferentiation and axonal outgrowth was tested in vitro, using human telencephalon neuroprogenitor cells and dorsal root ganglion explants, respectively. The CM from the three MSC populations induced neuronal differentiation from human neural progenitor cells, as well as neurite outgrowth from dorsal root ganglion explants. Moreover, all the MSC populations promoted the same extent of neurodifferentiation, while ASC CM demonstrated higher potential in promoting axonal growth.



中文翻译:

利用从不同组织来源分离的MSC的分泌组对神经元分化和轴突生长的影响

最近已经提出了使用间充质干细胞(MSC)分泌组进行细胞移植,作为中枢神经系统相关疾病的一种可能的基于游离的疗法。MSC分泌蛋白富含多种生物因子,可协同作用于受损组织的修复,因此使其成为再生应用的理想候选者。当前正在付出巨大的努力来绘制组成MSC分泌组的分子的图谱。我们的小组先前对脂肪组织(ASC),骨髓(BMSC)和脐带(HUCPVC)来源的MSC的分泌蛋白(以条件培养基-CM的形式)进行了蛋白质组学表征,其中涉及神经保护的蛋白质,确定了神经源性,神经分化,轴突导向和生长功能。此外,我们发现几种分子的表达之间存在显着差异,这可能表明它们的治疗结果可能不同。考虑到这一点,在本研究中,测试了ASC,BMSC和HUCPVC CM在促进神经分化和轴突生长方面的神经调节潜能。在体外,分别使用人端脑神经祖细胞和背根神经节外植体。来自三个MSC群体的CM诱导了人类神经祖细胞的神经元分化,以及背根神经节外植体的神经突生长。此外,所有的MSC群体都促进了相同程度的神经分化,而ASC CM在促进轴突生长方面显示出更高的潜力。

更新日期:2018-08-02
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