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静脉输注间充质干细胞改变急性脊髓损伤大鼠模型运动皮层的基因表达。

Intravenous Infusion of Mesenchymal Stem Cells Alters Motor Cortex Gene Expression in a Rat Model of Acute Spinal Cord Injury.

机构信息

1 Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.

2 Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.

出版信息

J Neurotrauma. 2019 Feb 1;36(3):411-420. doi: 10.1089/neu.2018.5793. Epub 2018 Aug 10.

Abstract

Recent evidence has demonstrated that remote responses in the brain, as well as local responses in the injured spinal cord, can be induced after spinal cord injury (SCI). Intravenous infusion of mesenchymal stem cells (MSCs) has been shown to provide functional improvements in SCI through local therapeutic mechanisms that provide neuroprotection, stabilization of the blood-spinal cord barrier, remyelination, and axonal sprouting. In the present study, we examined the brain response that might be associated with the functional improvements induced by the infused MSCs after SCI. Genome-wide RNA profiling was performed in the motor cortex of SCI rats at 3 days post-MSC or vehicle infusion. Then, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) data revealed that the "behaviorally-associated differentially expressed genes (DEGs)" were identified by the Pearson's correlation analysis with the behavioral function, suggesting that the "behaviorally-associated DEGs" may be related to the functional recovery after systemic infusion of MSCs in SCI. These results suggested that the infused MSCs alter the gene expression signature in the brain and that these expression changes may contribute to the improved function in SCI.

摘要

最近的证据表明,脊髓损伤(SCI)后,大脑的远程反应以及受损脊髓的局部反应都可以被诱导。静脉输注间充质干细胞(MSCs)已被证明可以通过局部治疗机制改善 SCI 的功能,这些机制提供神经保护、稳定血脊髓屏障、髓鞘再生和轴突发芽。在本研究中,我们研究了与 SCI 后输注 MSCs 诱导的功能改善相关的大脑反应。在 MSC 或载体输注后 3 天,对 SCI 大鼠的运动皮层进行了全基因组 RNA 谱分析。然后,定量逆转录聚合酶链反应(qRT-PCR)数据显示,通过与行为功能的 Pearson 相关分析鉴定了“与行为相关的差异表达基因(DEGs)”,表明“与行为相关的 DEGs”可能与全身输注 MSC 后 SCI 的功能恢复有关。这些结果表明,输注的 MSCs 改变了大脑中的基因表达特征,这些表达变化可能有助于改善 SCI 的功能。

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