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脂肪间充质干细胞移植在多发性硬化症的 cuprizone 模型中促进髓鞘再生。

Promotion of remyelination by adipose mesenchymal stem cell transplantation in a cuprizone model of multiple sclerosis.

机构信息

1. Department of Anatomical Sciences, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Cell J. 2013 Summer;15(2):142-51. Epub 2013 Jul 2.

Abstract

OBJECTIVE

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). Stem cell transplantation is a new therapeutic approach for demyelinating diseases such as MS which may promote remyelination. In this study, we evaluate the remyelinating potential of adipose mesenchymal stem cells (ADSCs) and their effect on neural cell composition in the corpus callosum in an experimental model of MS.

MATERIALS AND METHODS

This experimental study used adult male C57BL/6 mice. Cultured ADSCs were confirmed to be CD73(+),CD90(+), CD31(-),CD45(-), and labeled by PKH26. Animals were fed with 0.2% w/w cuprizone added to ground breeder chow ad libitum for six weeks. At day 0 after cuprizone removal, mice were randomly divided into two groups: the ADSCs-transplanted group and the control vehicle group (received medium alone). Some mice of the same age were fed with their normal diet to serve as healthy control group. Homing of ADSCs in demyelinated lesions was examined by fluorescent microscope. At ten days after transplantation, the mice were euthanized and their cells analyzed by luxol fast blue staining (LFB), transmission electron microscopy and flow cytometry. Results were analyzed by one-way analysis of variance (ANOVA).

RESULTS

According to fluorescent cell labeling, transplanted ADSCs appeared to survive and exhibited homing specificity. LFB staining and transmission electron microscope evaluation revealed enhanced remyelination in the transplanted group compared to the control vehicle group. Flow cytometry analysis showedan increase in Olig2 and O4 cells and a decrease in GFAP and Iba-1 cells in the transplanted group.

CONCLUSION

Our results indicate that ADSCs may provide a feasible, practical way for remyelination in diseases such as MS.

摘要

目的

多发性硬化症(MS)是一种中枢神经系统(CNS)的免疫介导性脱髓鞘疾病。干细胞移植是一种治疗脱髓鞘疾病(如 MS)的新方法,它可能促进髓鞘再生。在本研究中,我们评估了脂肪间充质干细胞(ADSCs)在 MS 实验模型中的髓鞘再生潜力及其对胼胝体神经细胞组成的影响。

材料和方法

本实验研究使用成年雄性 C57BL/6 小鼠。培养的 ADSCs 被确认为 CD73(+)、CD90(+)、CD31(-)、CD45(-),并用 PKH26 标记。动物自由摄入添加 0.2% w/w 剂量的 Cuprizone 的基础饲料,持续 6 周。在 Cuprizone 去除后的第 0 天,将小鼠随机分为 ADSC 移植组和对照组(仅接受培养基)。相同年龄的一些小鼠用正常饮食喂养作为健康对照组。通过荧光显微镜检查 ADSC 在脱髓鞘病变中的归巢情况。移植后 10 天,处死小鼠,用卢索快速蓝染色(LFB)、透射电镜和流式细胞术分析其细胞。结果采用单因素方差分析(ANOVA)进行分析。

结果

根据荧光细胞标记,移植的 ADSC 似乎存活并表现出归巢特异性。LFB 染色和透射电镜评价显示,与对照组相比,移植组的髓鞘再生增强。流式细胞术分析显示,移植组的 Olig2 和 O4 细胞增加,GFAP 和 Iba-1 细胞减少。

结论

我们的结果表明,ADSCs 可能为 MS 等疾病的髓鞘再生提供一种可行、实用的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b78d/3712775/8d03f455bdfc/Cell-J-15-142-g01.jpg

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