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静脉注射间充质干细胞对6-羟基多巴胺诱导的大鼠多巴胺能神经退行性变和胶质细胞活化具有治疗作用。

Intravenous mesenchymal stem cell administration exhibits therapeutic effects against 6-hydroxydopamine-induced dopaminergic neurodegeneration and glial activation in rats.

作者信息

Suzuki Syuuichirou, Kawamata Jun, Iwahara Naotoshi, Matsumura Akihiro, Hisahara Shin, Matsushita Takashi, Sasaki Masanori, Honmou Osamu, Shimohama Shun

机构信息

Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan.

Department of Neurology, Yale University School of Medicine, New Haven, USA.

出版信息

Neurosci Lett. 2015 Jan 1;584:276-81. doi: 10.1016/j.neulet.2014.10.039. Epub 2014 Nov 1.

Abstract

To explore a novel therapy against Parkinson's disease (PD), we evaluated the therapeutic effects of human bone marrow-derived mesenchymal stem cells (hBM-MSCs), pluripotent stromal cells with secretory potential of various neurotrophic and anti-inflammatory factors, in a hemi-parkinsonian rat model. The unilateral intrastriatal 6-hydroxydopamine (6-OHDA)-lesioned rats were injected hBM-MSCs (1.0 × 10(7)cells) or PBS intravenously 16 days after lesioning. Administration of hBM-MSCs inhibited methamphetamine-stimulated rotational behavior at 7, 14, 21 and 28 days after transplantation. Immunohistochemical analysis also showed that number of TH-positive neurons in the substantia nigra pars compacta was significantly preserved in hBM-MSCs-transplanted rats compared to sham-operated rats, whereas the immunoreactivity of ionized calcium binding adaptor molecule 1 was markedly inhibited. In this study, we demonstrated the therapeutic effects of intravenous hBM-MSCs administration in parkinsonian model rats presenting distinct parkinsonian phenotype at 16 days after 6-OHDA lesioning. The favorable findings raise the possibility that hBM-MSCs could be a novel therapeutic option to promote survival of dopaminergic neurons in PD.

摘要

为探索一种针对帕金森病(PD)的新型治疗方法,我们在半帕金森病大鼠模型中评估了人骨髓间充质干细胞(hBM-MSCs)的治疗效果,hBM-MSCs是具有分泌多种神经营养因子和抗炎因子潜力的多能基质细胞。在单侧纹状体内注射6-羟基多巴胺(6-OHDA)造模16天后,给大鼠静脉注射hBM-MSCs(1.0×10⁷个细胞)或磷酸盐缓冲液(PBS)。移植后7、14、21和28天,hBM-MSCs给药抑制了甲基苯丙胺刺激的旋转行为。免疫组织化学分析还显示,与假手术大鼠相比,hBM-MSCs移植大鼠黑质致密部中酪氨酸羟化酶(TH)阳性神经元的数量得到了显著保留,而离子钙结合衔接分子1的免疫反应性则受到明显抑制。在本研究中,我们证明了在6-OHDA损伤16天后呈现明显帕金森病表型的帕金森病模型大鼠中,静脉注射hBM-MSCs具有治疗效果。这些有利发现增加了hBM-MSCs可能成为促进PD中多巴胺能神经元存活的新型治疗选择的可能性。

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