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人神经干细胞移植入新生大鼠脑内后的时空动力学、分化及活力。

Spatio-temporal dynamics, differentiation and viability of human neural stem cells after implantation into neonatal rat brain.

机构信息

In-Vivo-NMR Laboratory, Max Planck Institute for Neurological Research, Gleuelerstrasse 50, D-50931 Cologne, Germany.

出版信息

Eur J Neurosci. 2011 Aug;34(3):382-93. doi: 10.1111/j.1460-9568.2011.07759.x. Epub 2011 Jun 27.


DOI:10.1111/j.1460-9568.2011.07759.x
PMID:21707793
Abstract

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.

摘要

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。

相似文献

[1]
Spatio-temporal dynamics, differentiation and viability of human neural stem cells after implantation into neonatal rat brain.

Eur J Neurosci. 2011-6-27

[2]
Survival, migration and neuronal differentiation of human fetal striatal and cortical neural stem cells grafted in stroke-damaged rat striatum.

Eur J Neurosci. 2007-8

[3]
Human fetal cortical and striatal neural stem cells generate region-specific neurons in vitro and differentiate extensively to neurons after intrastriatal transplantation in neonatal rats.

J Neurosci Res. 2006-12

[4]
A DNA hybridization system for labeling of neural stem cells with SPIO nanoparticles for MRI monitoring post-transplantation.

Biomaterials. 2015-4-3

[5]
Mesenchymal and neural stem cells labeled with HEDP-coated SPIO nanoparticles: in vitro characterization and migration potential in rat brain.

Brain Res. 2009-2-19

[6]
Detection of neural stem cells function in rats with traumatic brain injury by manganese-enhanced magnetic resonance imaging.

Chin Med J (Engl). 2011-6

[7]
Survival, integration, and differentiation of neural stem cell lines after transplantation to the adult rat striatum.

Exp Neurol. 1997-6

[8]
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Brain Res. 2004-8-6

[9]
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Exp Neurol. 2002-5

[10]
Folic acid stimulates proliferation of transplanted neural stem cells after focal cerebral ischemia in rats.

J Nutr Biochem. 2013-7-11

引用本文的文献

[1]
Magnetic resonance imaging of human neural stem cells in rodent and primate brain.

Stem Cells Transl Med. 2021-1

[2]
In vivo Cell Tracking Using Non-invasive Imaging of Iron Oxide-Based Particles with Particular Relevance for Stem Cell-Based Treatments of Neurological and Cardiac Disease.

Mol Imaging Biol. 2020-12

[3]
Comparative strategies for stem cell biodistribution in a preclinical study.

Acta Pharmacol Sin. 2019-11-8

[4]
D-mannose-Coating of Maghemite Nanoparticles Improved Labeling of Neural Stem Cells and Allowed Their Visualization by MRI after Transplantation in the Mouse Brain.

Cell Transplant. 2019-7-11

[5]
Individual Profiles of Microglia Polarization After Stroke, Represented by the Genes iNOS and Ym1.

Front Immunol. 2019-6-4

[6]
Persistent Quantitative Vitality of Stem Cell Graft Is Necessary for Stabilization of Functional Brain Networks After Stroke.

Front Neurol. 2019-4-5

[7]
Methodological aspects of MRI of transplanted superparamagnetic iron oxide-labeled mesenchymal stem cells in live rat brain.

PLoS One. 2017-10-19

[8]
Ferumoxytol Labeling of Human Neural Progenitor Cells for Diagnostic Cellular Tracking in the Porcine Spinal Cord with Magnetic Resonance Imaging.

Stem Cells Transl Med. 2016-8-29

[9]
In Vivo Non-Invasive Tracking of Macrophage Recruitment to Experimental Stroke.

PLoS One. 2016-6-24

[10]
Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation.

Int J Nanomedicine. 2016-4-27

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