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将CG4少突胶质细胞祖细胞移植到髓鞘缺乏的大鼠脑内会导致轴突髓鞘形成并增强少突胶质细胞标志物。

Transplantation of CG4 oligodendrocyte progenitor cells in the myelin-deficient rat brain results in myelination of axons and enhanced oligodendroglial markers.

作者信息

Espinosa de los Monteros A, Zhao P, Huang C, Pan T, Chang R, Nazarian R, Espejo D, de Vellis J

机构信息

Department of Neurobiology, Mental Retardation Research Center, Neuropsychiatric Institute, UCLA School of Medicine, Los Angeles, California 90024, USA.

出版信息

J Neurosci Res. 1997 Dec 1;50(5):872-87. doi: 10.1002/(SICI)1097-4547(19971201)50:5<872::AID-JNR23>3.0.CO;2-1.

Abstract

Transplantation of oligodendrocyte (Ol) progenitor cells into the central nervous system is a promising approach for the treatment of myelin disorders. This approach requires providing adequate numbers of healthy cells with myelinating potential. We recently showed the successful transplantation of Ol progenitors into the myelin-deficient (md) rat brain. In the present work, CG4 cells, a cell line with properties of Ol progenitors, were labeled with fast blue and grafted into P3-P5 pups born to carrier mothers. Examination of host brains 2 weeks posttransplant indicated that CG4 cells display a much more extensive migration capacity than their wild-type counterparts. These cells synthesized myelin components. In addition, ultrastructural analysis showed myelin formation along axons of md hosts in various brain regions, including corpus callosum, cerebellum, and brainstem. Furthermore, in situ hybridization studies performed on sagittal sections revealed extensive expression of transferrin-mRNA within the md host parenchyma. The high survival and functional features displayed by CG4 cells after transplantation, together with their striking wide distribution within the host parenchyma, as assessed by the presence of myelinated fibers in mutant hosts, emphasizes the importance of using highly motile and proliferative Ol progenitor cells. Strategies to improve the condition and life span of md rat pups are currently under investigation.

摘要

将少突胶质细胞(Ol)祖细胞移植到中枢神经系统是治疗髓鞘疾病的一种很有前景的方法。这种方法需要提供足够数量具有髓鞘形成潜力的健康细胞。我们最近展示了将Ol祖细胞成功移植到髓鞘缺陷(md)大鼠脑内。在本研究中,具有Ol祖细胞特性的细胞系CG4细胞用快蓝标记,并移植到携带该细胞系的母鼠所生的P3 - P5幼鼠体内。移植后2周对宿主脑的检查表明,CG4细胞比其野生型对应细胞表现出更广泛的迁移能力。这些细胞合成了髓鞘成分。此外,超微结构分析显示,在包括胼胝体、小脑和脑干在内的不同脑区,md宿主的轴突周围有髓鞘形成。此外,对矢状切片进行的原位杂交研究显示,md宿主实质内转铁蛋白 - mRNA广泛表达。通过突变宿主中有髓鞘纤维的存在评估,CG4细胞移植后显示出高存活率和功能特性,以及它们在宿主实质内显著广泛的分布,这强调了使用具有高迁移性和增殖能力的Ol祖细胞的重要性。目前正在研究改善md幼鼠状况和寿命的策略。

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