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人牙髓干细胞移植可补偿亨廷顿病 3-硝基丙酸大鼠模型纹状体萎缩并调节神经炎症。

Transplantation of human dental pulp stem cells compensates for striatal atrophy and modulates neuro-inflammation in 3-nitropropionic acid rat model of Huntington's disease.

机构信息

Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland.

出版信息

Neurosci Res. 2021 Sep;170:133-144. doi: 10.1016/j.neures.2020.12.002. Epub 2020 Dec 22.

Abstract

Stem cell-based therapy has recently offered a promising alternative for the remedy of neurodegenerative disorders like Huntington's disease (HD). Herein, we investigated the potential ameliorative effects of implantation of dental pulp stem cells (DPSCs) in 3-nitropropionic acid (3-NP) rat models of HD. In this regard, human DPSCs were isolated, culture-expanded and implanted in rats lesioned with 3-NP. Post-transplantation examinations revealed that DPSCs were able to survive and augment motor skills and muscle activity. Histological analysis showed DPSCs treatment hampered the shrinkage of the striatum along with the inhibition of gliosis and microgliosis in the striatum of 3-NP rat models. We also detected the downregulation of Caspase-3 and pro-inflammatory cytokines such as TNF and IL-1β upon DPSCs grafting. Overall, these findings imply that the grafting of DPSCs could repair motor-skill impairment and induce neurogenesis, probably through the secretion of neurotrophic factors and the modulation of neuroinflammatory response in HD animal models.

摘要

基于干细胞的疗法最近为治疗亨廷顿病(HD)等神经退行性疾病提供了一种有前途的替代方法。在此,我们研究了牙髓干细胞(DPSCs)在 3-硝基丙酸(3-NP)HD 大鼠模型中的植入对疾病的潜在改善作用。为此,我们分离、培养和植入了人 DPSCs,使其在 3-NP 损伤的大鼠中受损。移植后检查显示,DPSCs 能够存活并增强运动技能和肌肉活动。组织学分析表明,DPSCs 治疗可阻止纹状体的萎缩,并抑制 3-NP 大鼠模型纹状体中的神经胶质增生和小胶质细胞增生。我们还发现,在 DPSCs 移植后,Caspase-3 和促炎细胞因子(如 TNF 和 IL-1β)的表达下调。总的来说,这些发现表明,DPSCs 的移植可以修复运动技能障碍并诱导神经发生,这可能是通过神经营养因子的分泌和对 HD 动物模型神经炎症反应的调节。

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