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超顺磁性氧化铁标记的间充质干细胞在亨廷顿病大鼠模型中的神经保护作用及磁共振成像

Neuroprotective effects and magnetic resonance imaging of mesenchymal stem cells labeled with SPION in a rat model of Huntington's disease.

作者信息

Moraes Louise, Vasconcelos-dos-Santos Andreia, Santana Fernando Cleber, Godoy Mariana Araya, Rosado-de-Castro Paulo Henrique, Azevedo-Pereira Ricardo Luiz, Cintra Wagner Monteiro, Gasparetto Emerson Leandro, Santiago Marcelo Felippe, Mendez-Otero Rosalia

机构信息

Centro de Ciências da Saúde, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.

出版信息

Stem Cell Res. 2012 Sep;9(2):143-55. doi: 10.1016/j.scr.2012.05.005. Epub 2012 May 29.

Abstract

Bone marrow mesenchymal stem cells (MSC) have been tested and proven effective in some neurodegenerative diseases, but their tracking after transplantation may be challenging. Our group has previously demonstrated the feasibility and biosafety of rat MSC labeling with iron oxide superparamagnetic nanoparticles (SPION). In this study, we investigated the therapeutic potential of SPION-labeled MSC in a rat model of Huntington's disease, a genetic degenerative disease with characteristic deletion of striatal GABAergic neurons. MSC labeled with SPION were injected into the striatum 1h after quinolinic acid injection. FJ-C analysis demonstrated that MSC transplantation significantly decreased the number of degenerating neurons in the damaged striatum 7 days after lesion. In this period, MSC transplantation enhanced the striatal expression of FGF-2 but did not affect subventricular zone proliferation, as demonstrated by Ki67 proliferation assay. In addition, MSC transplantation significantly reduced the ventriculomegaly in the lesioned brain. MRI and histological techniques detected the presence of the SPION-labeled cells at the lesion site. SPION-labeled MSC produced magnetic resonance imaging (MRI) signals that were visible for at least 60 days after transplantation. Our data highlight the potential of adult MSC to reduce brain damage under neurodegenerative diseases and indicate the use of nanoparticles in cell tracking, supporting their potential as valuable tools for cell therapy.

摘要

骨髓间充质干细胞(MSC)已在一些神经退行性疾病中进行了测试并被证明有效,但其移植后的追踪可能具有挑战性。我们的团队此前已证明用氧化铁超顺磁性纳米颗粒(SPION)标记大鼠MSC的可行性和生物安全性。在本研究中,我们研究了SPION标记的MSC在亨廷顿舞蹈病大鼠模型中的治疗潜力,亨廷顿舞蹈病是一种具有纹状体GABA能神经元特征性缺失的遗传性退行性疾病。在注射喹啉酸1小时后,将用SPION标记的MSC注射到纹状体中。FJ - C分析表明,MSC移植显著减少了损伤后7天受损纹状体中变性神经元的数量。在此期间,如Ki67增殖试验所示,MSC移植增强了纹状体中FGF - 2的表达,但不影响脑室下区的增殖。此外,MSC移植显著减少了受损大脑中的脑室扩大。MRI和组织学技术在损伤部位检测到了SPION标记的细胞。SPION标记的MSC产生的磁共振成像(MRI)信号在移植后至少60天可见。我们的数据突出了成年MSC在神经退行性疾病中减少脑损伤的潜力,并表明纳米颗粒在细胞追踪中的应用,支持了它们作为细胞治疗有价值工具的潜力。

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