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大鼠自体骨髓基质细胞移植入中枢神经系统的临床前评估模型

A pre-clinical assessment model of rat autogeneic bone marrow stromal cell transplantation into the central nervous system.

作者信息

Lee Jang-Bo, Kuroda Satoshi, Shichinohe Hideo, Yano Shunsuke, Kobayashi Hiroyuki, Hida Kazutoshi, Iwasaki Yoshinobu

机构信息

Department of Neurosurgery, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.

出版信息

Brain Res Brain Res Protoc. 2004 Nov;14(1):37-44. doi: 10.1016/j.brainresprot.2004.09.004.

DOI:10.1016/j.brainresprot.2004.09.004
PMID:15519950
Abstract

In order to verify the biological aspects of 'autogeneic' bone marrow stromal cells (BMSC) transplantation for neurological disorders, we aimed our study towards the assessment of the survival, distribution, and differentiation of autologous BMSC in the central nervous system (CNS). We harvested rat BMSC from femur bones, and the nuclei were then fluorescently labeled by a 24-h co-culture with bis-benzimide. These BMSC were stereotactically injected into the striatum (n=6) or thoracic cord (n=8) of each animal. We evaluated the distribution and differentiation of 'autogeneic' BMSC in the brain and spinal cord after 4 weeks, using the immunohistochemistry technique. We found some injected cells in the ipsilateral striatum, hippocampus, neocortex, and bilateral corpus callosum, and approximately 20% and 15% of the engrafted cells expressed neuronal and astrocytic markers, respectively. Other injected cells were distributed in the dorsal funiculus and adjacent gray matter, and about 10% and 15% of these cells expressed neuronal and astrocytic markers, respectively. Although the precise mechanism of BMSC transdifferentiation still remains unclear, the present results show that 'autogeneic' BMSC could highly differentiate into their own CNS neural cells, suggesting that they are surrounded by favorable conditions.

摘要

为了验证“自体”骨髓基质细胞(BMSC)移植治疗神经疾病的生物学特性,我们的研究旨在评估自体BMSC在中枢神经系统(CNS)中的存活、分布及分化情况。我们从大鼠股骨中采集BMSC,然后通过与双苯甲酰亚胺共培养24小时对细胞核进行荧光标记。将这些BMSC立体定向注射到每只动物的纹状体(n = 6)或胸段脊髓(n = 8)中。4周后,我们使用免疫组织化学技术评估“自体”BMSC在脑和脊髓中的分布及分化情况。我们在同侧纹状体、海马体、新皮层和双侧胼胝体中发现了一些注射的细胞,分别约有20%和15%的植入细胞表达神经元和星形胶质细胞标志物。其他注射的细胞分布在背侧索和相邻灰质中,这些细胞分别约有10%和15%表达神经元和星形胶质细胞标志物。尽管BMSC转分化的确切机制仍不清楚,但目前的结果表明,“自体”BMSC可以高度分化为自身的CNS神经细胞,这表明它们处于有利的条件下。

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