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首页> 外文期刊>The European Journal of Neuroscience >Integration and differentiation of neural stem cells after transplantation into the dysmyelinated central nervous system of adult mice.
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Integration and differentiation of neural stem cells after transplantation into the dysmyelinated central nervous system of adult mice.

机译:移植到成年小鼠的脱髓鞘的中枢神经系统后,神经干细胞的整合和分化。

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Abstract Mutant mice deficient in the myelin-associated glycoprotein (MAG) and the nonreceptor-type tyrosine kinase Fyn are characterized by a severely hypomyelinated central nervous system (CNS) and morphologically abnormal myelin sheaths. Despite this pronounced phenotype, MAG/Fyn-deficient mice have a normal longevity. In the present study, we took advantage of the normal life expectancy of this myelin mutant and grafted neural stem cells (NSCs) into the CNS of MAG/Fyn-deficient mice to study in short- and long-term experiments the fate of NSCs in adult dysmyelinated brains. Neural stem cells were isolated from spinal cords of transgenic mouse embryos ubiquitously expressing enhanced green fluorescent protein. Cells were expanded in vitro in the presence of mitogens for up to 5 weeks before they were grafted into the lateral ventricles or injected into white matter tracts. Analysis of mutant brains 3-15 weeks after intracerebroventricular transplantation of NSCs revealed only limited integration of donor cells into the host brains. However, injection of NSCs directly into white matter tracts resulted in widespread distribution of donor cells within the host tissue. Donor cells survived for at least 15 weeks in adult host brains. The majority of grafted cells populated white matter tracts and differentiated into oligodendrocytes that myelinated host axons. Results suggest that intraparenchymal transplantation of NSCs might be a strategy to reconstruct myelin in dysmyelinated adult brains.
机译:摘要缺乏髓鞘相关糖蛋白(MAG)和非受体型酪氨酸激酶Fyn的突变小鼠具有严重的髓鞘低下的中枢神经系统(CNS)和形态异常的髓鞘。尽管有这种明显的表型,但MAG / Fyn缺陷型小鼠却具有正常的寿命。在本研究中,我们利用这种髓磷脂突变体的正常预期寿命,并将神经干细胞(NSC)移植到MAG / Fyn缺陷小鼠的CNS中,在短期和长期实验中研究NSC的命运。成年性髓鞘异常的大脑。从普遍表达增强的绿色荧光蛋白的转基因小鼠胚胎的脊髓中分离出神经干细胞。在有丝分裂原存在的情况下,将细胞体外扩增长达5周,然后将其移植到侧脑室或注射到白质束中。对脑室内移植NSC的3到15周后的突变脑进行分析后发现,供体细胞只能有限地整合到宿主脑中。但是,将NSC直接注射到白质束中会导致供体细胞在宿主组织内广泛分布。供体细胞在成年宿主脑中存活至少15周。大部分移植细胞遍布白质区,并分化为使宿主轴突有髓鞘的少突胶质细胞。结果表明,NSCs的实质内移植可能是在有髓鞘异常的成年大脑中重建髓鞘的策略。

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