中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (4): 509-517.doi: 10.4103/1673-5374.204999

• 综述:神经损伤修复保护与再生 •    下一篇

内源性神经干细胞能改善髓磷脂再生吗?

  

  • 收稿日期:2017-04-10 出版日期:2017-04-15 发布日期:2017-04-15
  • 基金资助:

    此项研究由德国学术交流中心(DAAD)、德国研究委员会(DFG; SPP1757/KU1934/2_1, KU1934/5-1)、克里斯蒂安-克劳迪亚·亨佩尔临床干细胞研究YoungGlia基金会、沃尔特-伊尔斯玫瑰基金会、詹姆斯-伊丽莎白克洛彭堡、皮克-克洛彭堡杜塞尔多夫基金会共同赞助

Heterogeneous populations of neural stem cells contribute to myelin repair

Rainer Akkermann, Felix Beyer, Patrick Küry   

  1. Neuroregeneration Laboratory, Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany
  • Received:2017-04-10 Online:2017-04-15 Published:2017-04-15
  • Contact: Patrick Küry, Ph.D., kuery@uni-duesseldorf.de.
  • Supported by:

    The German Academic Exchange Service (DAAD) supported RA. This work was also supported by grants to PK by the German Research Council (DFG; SPP1757/KU1934/2_1, KU1934/5-1), the Christiane and Claudia Hempel Foundation for clinical stem cell research and YoungGlia. The MS Center at the Department of Neurology is supported in part by the Walter and Ilse Rose Foundation and the James and Elisabeth Cloppenburg, Peek & Cloppenburg Du?sseldorf Foundation.

摘要:

作为自然的造物,哺乳动物神经系统内髓鞘十分精巧,而这种特殊脂质结构的损伤可以是致命的。长期丧失电绝缘以及髓鞘提供给轴突的进一步支持性功能,如脱髓鞘疾病多发性硬化所见,会导致神经变性并导致进行性残疾。多种证据表明不断增加的少突胶质细胞前体细胞(OPCs)可以代替丢失的少突胶质细胞(OLs)以恢复丢失的髓磷脂。许多研究致力于揭示这种再生缺陷的潜在原因,但尽管有许多有前景的方法,但至今未成功开发出髓鞘再生促进药物。除了OPCs,成人中枢神经系统的神经干细胞也具有产生髓鞘OL的高潜力。在脑中存在至少两个神经干细胞小生境,内侧脑室侧脑室和齿状回亚颗粒区的脑室下区,并且神经干细胞的另外来源位于脊髓中央管中。虽然大量的文献已经描述了它们的神经发生能力,但是关于这些细胞的少突胶质细胞潜力仍然知之甚少,即使一些动物研究提供了它们对髓鞘再生作用的研究证据。本文总结和讨论了这些研究,考虑到不同的基质,干细胞生态位之间异质性和目前当前的策略,文中报道了如何促进干细胞介导的髓鞘修复。

ORCID:0000-0003-1583-9987(Rainer Akkermann);0000-0002-3329-0249(Felix Beyer);0000-0002-2654-1126(Patrick Küry)

Abstract:

be damage to this specialized lipid structure. Long-term loss of electrical insulation and of further supportive functions myelin provides to axons, as seen in demyelinating diseases such as multiple sclerosis (MS), leads to neurodegeneration and results in progressive disabilities. Multiple lines of evidence have demonstrated the increasing inability of oligodendrocyte precursor cells (OPCs) to replace lost oligodendrocytes (OLs) in order to restore lost myelin. Much research has been dedicated to reveal potential reasons for this regeneration deficit but despite promising approaches no remyelination-promoting drugs have successfully been developed yet. In addition to OPCs neural stem cells of the adult central nervous system also hold a high potential to generate myelinating OLs. There are at least two neural stem cell niches in the brain, the subventricular zone lining the lateral ventricles and the subgranular zone of the dentate gyrus, and an additional source of neural stem cells has been located in the central canal of the spinal cord. While a substantial body of literature has described their neurogenic capacity, still little is known about the oligodendrogenic potential of these cells, even if some animal studies have provided proof of their contribution to remyelination. In this review, we summarize and discuss these studies, taking into account the different niches, the heterogeneity within and between stem cell niches and present current strategies of how to promote stem cell-mediated myelin repair.

Key words: heterogeneity, oligodendrocyte, neuroregeneration, multiple sclerosis, inhibitors, intracellular protein localization, adult neural stem cell niche, remyelination