In-Vivo-NMR Laboratory, Max Planck Institute for Neurological Research, Gleuelerstrasse 50, D-50931 Cologne, Germany.
Eur J Neurosci. 2011 Aug;34(3):382-93. doi: 10.1111/j.1460-9568.2011.07759.x. Epub 2011 Jun 27.
Neural stem cells (NSCs) have attracted major research interest due to their potential use in cell replacement therapy. In patients, human cells are the preferred choice, one source of human NSCs being the brain of fetuses. The aims of the present study were to explore the long-term differentiation, mobility and viability of NSCs derived from the human fetal striatum in response to intracerebral implantation. To investigate long-term spatio-temporal and functional dynamics of grafts in vivo by magnetic resonance imaging, these cells were labeled with superparamagnetic iron oxide (SPIO) nanoparticles prior to implantation. SPIO-labeling of human NSCs left the quantitative profile of the proliferation, cell composition and differentiation capacity of the cells in vitro unaltered. Also after transplantation, the phenotypes after long-term cell differentiation were not significantly different from naïve cells. Upon transplantation, we detected a hypointensity corresponding to the striatal graft location in all animals and persisting for at least 4 months. The hypointense signal appeared visually similar both in location and in volume over time. However, quantitative volumetric analysis showed that the detectable, apparent graft volume decreased significantly from 3 to 16 weeks. Finally, the human NSCs were not proliferating after implantation, indicating lack of tumor formation. These cells are thus a promising candidate for translationally relevant investigations for stem cell-based regenerative therapies.
神经干细胞(NSCs)由于其在细胞替代治疗中的潜在用途而引起了主要的研究兴趣。在患者中,首选人类细胞,人类 NSCs 的一个来源是胎儿的大脑。本研究的目的是探索源自人胎脑纹状体的 NSCs 在脑内植入后的长期分化、迁移和活力。为了通过磁共振成像研究体内移植物的长期时空和功能动态,在植入前将这些细胞用超顺磁氧化铁(SPIO)纳米颗粒标记。SPIO 标记的人 NSCs 不会改变细胞体外增殖、细胞组成和分化能力的定量特征。即使在移植后,长期细胞分化后的表型与原始细胞也没有明显差异。移植后,我们在所有动物中均检测到与纹状体移植物位置相对应的低信号强度,且至少持续 4 个月。随着时间的推移,低信号在位置和体积上均视觉上相似。然而,定量体积分析显示,从 3 周到 16 周,可检测到的明显移植物体积显著减少。最后,植入后人类 NSCs 没有增殖,表明没有肿瘤形成。因此,这些细胞是用于基于干细胞的再生治疗的转化相关研究的有前途的候选物。
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