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骨髓间充质干细胞对铜诱导脱髓鞘的影响。

Effects of murine and human bone marrow-derived mesenchymal stem cells on cuprizone induced demyelination.

机构信息

Department of Neurology, Hannover Medical School, Hannover, Germany.

出版信息

PLoS One. 2013 Jul 26;8(7):e69795. doi: 10.1371/journal.pone.0069795. Print 2013.

Abstract

For the treatment of patients with multiple sclerosis there are no regenerative approaches to enhance remyelination. Mesenchymal stem cells (MSC) have been proposed to exert such regenerative functions. Intravenous administration of human MSC reduced the clinical severity of experimental autoimmune encephalomyelitis (EAE), an animal model mimicking some aspects of multiple sclerosis. However, it is not clear if this effect was achieved by systemic immunomodulation or if there is an active neuroregeneration in the central nervous system (CNS). In order to investigate remyelination and regeneration in the CNS we analysed the effects of intravenously and intranasally applied murine and human bone marrow-derived MSC on cuprizone induced demyelination, a toxic animal model which allows analysis of remyelination without the influence of the peripheral immune system. In contrast to EAE no effects of MSC on de- and remyelination and glial cell reactions were found. In addition, neither murine nor human MSC entered the lesions in the CNS in this toxic model. In conclusion, MSC are not directed into CNS lesions in the cuprizone model where the blood-brain-barrier is intact and thus cannot provide support for regenerative processes.

摘要

对于多发性硬化症患者,目前尚无促进髓鞘再生的再生方法。间充质干细胞(MSC)被提议发挥这种再生功能。静脉内给予人 MSC 可降低实验性自身免疫性脑脊髓炎(EAE)的临床严重程度,EAE 是一种模拟多发性硬化症某些方面的动物模型。然而,尚不清楚这种效果是通过全身免疫调节还是中枢神经系统(CNS)中的主动神经再生来实现的。为了研究中枢神经系统中的髓鞘再生和再生,我们分析了静脉内和经鼻给予的鼠和人骨髓来源 MSC 对杯状内毒素诱导的脱髓鞘的影响,杯状内毒素是一种毒性动物模型,可在不影响周围免疫系统的情况下分析髓鞘再生。与 EAE 相反,MSC 对脱髓鞘和髓鞘再生以及神经胶质细胞反应均无影响。此外,在这种毒性模型中,无论是鼠源 MSC 还是人源 MSC 均未进入中枢神经系统的病变部位。总之,在血脑屏障完整的杯状内毒素模型中,MSC 不会进入中枢神经系统病变部位,因此不能为再生过程提供支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d24a/3724887/e3e5a4b2289c/pone.0069795.g001.jpg

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