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神经化间充质干细胞 (NMSC) 表现出神经元转分化的表型和生物学证据,比未修饰的 MSC 更有效地抑制 EAE。

Neuralized mesenchymal stem cells (NMSC) exhibit phenotypical, and biological evidence of neuronal transdifferentiation and suppress EAE more effectively than unmodified MSC.

机构信息

Unit of Neuroimmunology and Multiple Sclerosis Center, Neurology department and The Agnes-Ginges Center for Neurogenetics, Hadassah University Hospital, Jerusalem, Ein-Kerem, Israel.

Unit of Neuroimmunology and Multiple Sclerosis Center, Neurology department and The Agnes-Ginges Center for Neurogenetics, Hadassah University Hospital, Jerusalem, Ein-Kerem, Israel.

出版信息

Immunol Lett. 2019 Aug;212:6-13. doi: 10.1016/j.imlet.2019.05.009. Epub 2019 May 30.

Abstract

In the last decade several studies employing stem cells-based therapies have been investigated as an optional treatment for multiple sclerosis. Several preclinical and few clinical studies tested the efficacy of mesenchymal stem cells as a potent candidate for such therapies. Here we suggest the option of "neuralization" of classical mesenchymal stem cells as a cellular structure that resembles neural stem cells as well as there differentiation by a unique procedure towards terminally differentiated neural cells suggesting that this cell population may be appropriate for clinical application in the CNS. We investigated whether neuralized MSC (NMSC) could promote repair and recovery after injection into mice with EAE. Injection of NMSC and differentiated NMSC starting at the onset of the chronic phase of disease improved neurological function compared to controls as well as compared to naïve MSC. Injection of NMSC and mainly differentiated correlated with a reduction in the inflammation as well as in the axonal loss/damage and reduced area of demyelination. These observations suggest that NMSC and differentiated NMSC may suggest a more potent cell-based therapy that naïve MSC in the treatment arsenal of multiple sclerosis.

摘要

在过去的十年中,已经有几项使用基于干细胞的治疗方法的研究被探索作为多发性硬化症的一种可选治疗方法。一些临床前和少数临床研究测试了间充质干细胞作为这种治疗的有效候选物的功效。在这里,我们建议将经典间充质干细胞“神经化”作为一种类似于神经干细胞的细胞结构,并通过一种独特的程序向终末分化的神经细胞分化,这表明这种细胞群体可能适合在中枢神经系统中的临床应用。我们研究了神经化的 MSC(NMSC)是否可以在患有 EAE 的小鼠中注射后促进修复和恢复。与对照组以及与未分化的 MSC 相比,在疾病慢性期开始时注射 NMSC 和分化的 NMSC 可改善神经功能。NMSC 和主要分化的注射与炎症的减少以及轴突损失/损伤的减少和脱髓鞘面积的减少相关。这些观察结果表明,NMSC 和分化的 NMSC 可能提示一种更有效的基于细胞的治疗方法,而不是多发性硬化症治疗武器库中的未分化 MSC。

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