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脑室腔内移植诱导分泌神经营养因子的人骨髓间充质干细胞可减轻多发性硬化症小鼠模型的临床症状。

Intracerebroventricular transplantation of human mesenchymal stem cells induced to secrete neurotrophic factors attenuates clinical symptoms in a mouse model of multiple sclerosis.

机构信息

Felsenstein Medical Research Center, Tel Aviv University, Sackler School of Medicine, Petach Tikva, 49100, Israel.

出版信息

J Mol Neurosci. 2010 May;41(1):129-37. doi: 10.1007/s12031-009-9302-8. Epub 2009 Nov 10.

Abstract

Stem cell-based therapy holds great potential for future treatment of multiple sclerosis (MS). Bone marrow mesenchymal stem cells (MSCs) were previously reported to ameliorate symptoms in mouse MS models (experimental autoimmune encephalomyelitis, EAE). In this study, we induced MSCs to differentiate in vitro into neurotrophic factor-producing cells (NTFCs). Our main goal was to examine the clinical use of NTFCs on EAE symptoms. The NTFCs and MSCs were transplanted intracerebroventricularly (ICV) to EAE mice. We found that NTFCs transplantations resulted in a delay of symptom onset and increased animal survival. Transplantation of MSCs also exerted a positive effect but to a lesser extent. In vitro analysis demonstrated the NTFCs' capacity to suppress mice immune cells and protect neuronal cells from oxidative insult. Our results indicate that NTFCs-transplanted ICV delay disease symptoms of EAE mice, possibly via neuroprotection and immunomodulation, and may serve as a possible treatment to MS.

摘要

基于干细胞的疗法为多发性硬化症(MS)的未来治疗提供了巨大的潜力。骨髓间充质干细胞(MSCs)先前被报道可改善实验性自身免疫性脑脊髓炎(EAE)小鼠模型的症状。在这项研究中,我们诱导 MSCs 在体外分化为产生神经营养因子的细胞(NTFCs)。我们的主要目标是研究 NTFCs 对 EAE 症状的临床应用。将 NTFCs 和 MSCs 经脑室(ICV)移植到 EAE 小鼠中。我们发现 NTFCs 移植可延迟症状发作并提高动物存活率。MSC 移植也有积极作用,但程度较小。体外分析表明,NTFCs 具有抑制小鼠免疫细胞的能力,并能保护神经元细胞免受氧化损伤。我们的结果表明,脑室移植 NTFCs 可延迟 EAE 小鼠的疾病症状,可能通过神经保护和免疫调节,可作为 MS 的一种可能治疗方法。

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