Ectoderm mesenchymal stem cells promote differentiation and maturation of oligodendrocyte precursor cells

Ectoderm mesenchymal stem cells promote differentiation and maturation of oligodendrocyte precursor cells
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外胚层间充质干细胞促进少突胶质前体细胞分化成熟

DOI:
10.1016/j.bbrc.2016.10.115
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发表时间:
2016
影响因子:
3.1
通讯作者:
Xu Ximing
Xu Ximing
中科院分区:
生物学4区
文献类型:
--
作者:
Zhang Zhijian;Li Zhengnan;Deng Wenwen;He Qinghua;Wang Qiang;Shi Wentao;Chen Qian;Yang Wenjing;Spector Myron;Gong Aihua;Yu Jiangnan;Xu Ximing

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许多神经系统疾病都与少突胶质细胞的病理改变引起的脱髓鞘密切相关。虽然损伤后发生了内在髓鞘再生,但髓鞘化少突胶质细胞的再生效率仍有待提高。在此,我们报告了一个有价值的细胞来源,即神经嵴来源的外胚层间充质干细胞(EMSC),通过共培养少突胶质细胞前体细胞(OPCs)与EMSC促进少突胶质细胞分化和成熟的初步发现。结果表明,OPCs/EMSC共培养可显著增加少突胶质细胞突起的数量和长度,与单独培养OPCs和非接触OPCs/EMSC transwell培养相比,差异有显著性。此外,抑制实验表明,EMSC产生的可溶性因子Sonic hedgehog,间隙连接蛋白43和细胞外基质分子层粘连蛋白解释了促进OPC分化,因为抑制这三种蛋白中的任何一种的功能都会导致少突胶质细胞的突起和脱离的实质性收缩。OPCs/EMSC共培养体系是促进少突胶质细胞分化成熟的一个范例,EMSC有望成为治疗少突胶质细胞死亡和脱髓鞘引起的神经系统疾病的一个有前景的细胞来源。
Many neurological diseases are closely associated with demyelination caused by pathological changes of oligodendrocytes. Although intrinsic remyelination occurs after injury, the regeneration efficiency of myelinating oligodendrocytes remains to be improved. Herein, we reported an initiative finding of employing a valuable cell source, namely neural crest-derived ectoderm mesenchymal stem cells (EMSCs), for promoting oligodendrocyte differentiation and maturation by co-culturing oligodendrocyte precursor cells (OPCs) with the EMSCs. The results demonstrated that the OPCs/EMSCs co-culture could remarkably increase the number and length of oligodendrocyte processes in comparison with the mono-cultured OPCs and non-contact OPCs/EMSCs transwell culture. Furthermore, the inhibition experiments revealed that the EMSCs-produced soluble factor Sonic hedgehog, gap junction protein connexin 43 and extracellular matrix molecule laminin accounted for the promoted OPC differentiation since inhibiting the function of anyone of the three proteins led to substantial retraction of processes and detachment of oligodendrocytes. Altogether, OPCs/EMSCs co-culture system could be a paradigmatic approach for promoting differentiation and maturation of oligodendrocytes, and EMSCs will be a promising cell source for the treatment of neurological diseases caused by oligodendrocyte death and demyelination.