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The Effect of Cell Fusion with the Host Brain Cells on the Neuronal Differentiation of Transplanted Mesenchymal Stem Cells in the Brain

细胞与宿主脑细胞融合对脑内移植间充质干细胞神经元分化的影响

基本信息

批准号：
18591163
负责人：
TANAKA Akemi
金额：
$ 2.49万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Lysosomal storage disease (LSD) is a group of genetic diseases caused by deficiency of an enzyme for the catabolism in lysosome. Most of them show systemic accumulation of undigested substrates in lysosomes, which cause progressive diseases including the brain. Bone marrow transplantation and enzyme replacement therapy are clinically available as effective therapy for some LSDs. But the brain involvement is an exception. We transplanted fetal brain cells, cultured neuronal cells, or bone marrow derived mesenchymal stem cells into the ventricle of neonatal mouse brain to deliver the deficient enzyme and protect the brain from the disease, and studied the migrating area of the grafted cells and their viable period. β-Galactosidase knock-out mouse (GM1-gangliosidosis model mouse) and transgenic mouse expressing human β-galactosidase were used as the recipient and the donor, respectively. The cells of 0.5-1.0×10^5 were injected into the right-side ventricle on the 2nd day after birth. The treated mice were examined histologically by B-galactosidase activity staining (X-Gal) to see the grafted cell distribution, and ganglioside-GM1 immunostaining to examine the therapeutic effect. The injected cells were grafted on the surface of the right-side of ventricle one week after the injection. They migrated into the deep area of both hemisphere, and the number of X-Gal positive cells became 10-20 fold at two weeks after the injection. Intracerebral transplantation of some special cells would have a possibility of permanent cure of the brain in LSDs.

溶酶体积积症（LSD）是一组由溶酶体中的一种酶缺乏引起的遗传性疾病。它们中的大多数显示未消化的底物在溶酶体中的全身性积累，这导致包括脑在内的进行性疾病。骨髓移植和酶替代疗法在临床上可作为一些LSD的有效疗法。但大脑参与是个例外。我们将胎脑细胞、培养的神经元细胞或骨髓间充质干细胞移植到新生小鼠脑室内，以递送缺陷的酶并保护脑免受疾病的影响，并研究了移植细胞的迁移区域和存活期。以β-半乳糖苷酶基因敲除小鼠（GM 1-神经节苷脂沉积症模型小鼠）和表达人β-半乳糖苷酶的转基因小鼠分别作为受体和供体。于出生后第2天将0.5-1.0×10^5细胞注入右侧脑室。用β-半乳糖苷酶活性染色（X-Gal）观察移植细胞的分布，用神经节苷脂-GM 1免疫组化观察治疗效果。注射后1周将细胞移植于右心室表面。注射后2周，X-Gal阳性细胞数增加10-20倍。脑内移植某些特殊的细胞将有可能永久治愈LSD患者的大脑。