Introduction: The mechanism through which mesenchymal stromal cells (MSCs) enhance functional recovery in experimental models of stroke remains to be elucidated. This study was carried out to determine the microRNA (miRNA) profile elicited in response to MSC transplantation after stroke. Methods: This was an in vivo study on the effect of MSC transplantation on the exosomal miRNA profile in a rat model of middle cerebral artery occlusion (MCAO)-induced stroke. Eighteen male Sprague-Dawley rats were subjected to MCAO surgery (model group), and half received a transplantation of MSCs (model + MSC group) isolated from rat bone marrow. A sham-operated group (Sham) was included as a control. After 7 days, the volume of the brain lesion and severity of the functional impairments were measured. Exosomes were isolated from blood plasma samples for miRNA transcriptome analysis by Illumina sequencing. Results: The MCAO surgery successfully induced infarcts and neurological deficits in the rats, whereas the MSC transplantation significantly repaired these impairments. Illumina sequencing identified 764 known miRNAs, including 135 that were differentially expressed in common between the model + MSC and model, model and Sham, and model + MSC and Sham groups, respectively. Gene Ontology enrichment analysis revealed that the target genes of these miRNAs were associated with biological processes relevant to learning or memory and the development of the central and peripheral nervous systems. Pathway enrichment analysis identified a cluster of miRNAs (e.g., rno-miR-19b-3p, rno-miR-204-3p, rno-miR-125a-5p, rno-miR-672-3p, and rno-miR-667-3p) to be significantly related to the Janus kinase-signal transducer and activator of transcription, mechanistic target of rapamycin, phosphoinositide 3-kinases–Akt, and insulin signaling pathways via their control of their gene targets. Conclusion: We confirmed that MSC transplantation repaired stroke-induced functional impairments in rats by regulating various pathways associated with nervous system protection and MSC differentiation through the deregulation of exosomal miRNAs.
Neuroimmunomodulation

中文翻译：

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外泌体 MicroRNA 谱负责间充质基质细胞移植诱导的大鼠中风后功能恢复的改善

简介：间充质基质细胞 (MSCs) 在中风实验模型中增强功能恢复的机制仍有待阐明。本研究旨在确定中风后 MSC 移植引起的 microRNA (miRNA) 谱。方法：这是一项关于 MSC 移植对大脑中动脉闭塞 (MCAO) 诱导的中风大鼠模型中外泌体 miRNA 谱影响的体内研究。18只雄性Sprague-Dawley大鼠接受MCAO手术（模型组），一半接受大鼠骨髓分离的MSCs移植（模型+MSC组）。包括一个假手术组（Sham）作为对照。7天后，测量脑损伤的体积和功能障碍的严重程度。从血浆样品中分离外泌体，通过 Illumina 测序进行 miRNA 转录组分析。结果：MCAO 手术成功地诱导了大鼠的梗塞和神经功能缺损，而 MSC 移植显着修复了这些损伤。Illumina 测序鉴定了 764 个已知 miRNA，其中 135 个分别在模型 + MSC 和模型、模型和 Sham 以及模型 + MSC 和 Sham 组之间差异表达。基因本体富集分析表明，这些miRNA的靶基因与学习或记忆相关的生物学过程以及中枢和周围神经系统的发育有关。通路富集分析鉴定了一组 miRNA（例如，rno-miR-19b-3p、rno-miR-204-3p、rno-miR-125a-5p、rno-miR-672-3p 和 rno-miR-667- 3p) 与 Janus 激酶信号转导和转录激活因子显着相关，结论：我们证实，MSC 移植通过外泌体 miRNA 的失调来调节与神经系统保护和 MSC 分化相关的各种途径，从而修复了大鼠中风诱导的功能障碍。
神经免疫调节