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骨髓基质细胞和骨髓来源的单核细胞:哪一种适合作为移植治疗脑梗死模型鼠的细胞来源?

Bone marrow stromal cells and bone marrow-derived mononuclear cells: which are suitable as cell source of transplantation for mice infarct brain?

机构信息

Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

出版信息

Neuropathology. 2010 Apr;30(2):113-22. doi: 10.1111/j.1440-1789.2009.01050.x. Epub 2009 Sep 7.

Abstract

There are few studies that denote whether bone marrow stromal cells (BMSC) and bone marrow-derived mononuclear cells (MNC) show the same therapeutic effects, when directly transplanted into the infarct brain. This study therefore aimed to compare their biological properties and behaviors in the infarct brain. Mouse BMSC were harvested and cultured. Mouse MNC were obtained through centrifugation techniques. Their cell markers were analyzed with FACS analysis. The MNC (10(6) cells; n = 10) or BMSC (2 x 10(5) cells; n = 10) were stereotactically transplanted into the ipsilateral striatum of the mice subjected to permanent middle cerebral artery occlusion at 7 days after the insult. Their survival, migration, and differentiation in the infarct brain were precisely analyzed using immunohistochemistry 4 weeks after transplantation. The MNC were positive for CD34, CD45, CD90, but were negative for Sca-1. The BMSC were positive for CD90 and Sca-1. The transplanted BMSC, but not MNC, extensively migrated into the peri-infarct area. Approximately 20% of the transplanted BMSC expressed a neuronal marker, NeuN in the infarct brain, although only 1.4% of the transplanted MNC expressed NeuN. These findings strongly suggest that there are large, biological differences between MNC and BMSC as cell sources of regenerative medicine for ischemic stroke.

摘要

目前鲜有研究直接将骨髓基质细胞(BMSC)和骨髓单个核细胞(MNC)移植到梗死脑内,观察两者是否具有相同的治疗效果。因此,本研究旨在比较两者在梗死脑内的生物学特性和行为。从小鼠骨髓中分离培养 BMSC,通过离心技术获取 MNC,利用流式细胞术分析其细胞标志物。在脑缺血 7 天后,将 MNC(10(6) 个细胞;n = 10)或 BMSC(2 x 10(5) 个细胞;n = 10)立体定向移植到永久性大脑中动脉闭塞模型的同侧纹状体。移植 4 周后,通过免疫组织化学方法精确分析其在梗死脑内的存活、迁移和分化情况。MNC 表达 CD34、CD45、CD90,但不表达 Sca-1;BMSC 表达 CD90 和 Sca-1。移植的 BMSC 广泛迁移到梗死周边区,但 MNC 未见明显迁移。约 20%的移植 BMSC 在梗死脑内表达神经元标志物 NeuN,而移植的 MNC 中仅有 1.4%表达 NeuN。这些发现强烈表明,MNC 和 BMSC 作为缺血性脑卒中再生医学的细胞来源,其生物学特性存在显著差异。

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