Background

This study aimed to investigate the effect of microRNA 146a (miR-146a) overexpressed bone marrow mesenchymal stem cells (BMMSCs) exosomes on spinal cord injury (SCI) recovery.

Methods

Rat BMMSCs were isolated and transfected with miR-146a mimic (miR-mimic) and control mimic (NC-mimic), after which their exosomes were isolated. Afterward, SCI rat models were constructed, then treated with phosphate buffer saline (PBS), NC BMMSCs exosomes (separated from the culture medium of BMMSCs with NC-mimic), and miR-146a overexpressed BMMSCs exosomes (isolated from the culture medium of BMMSCs with miR-mimic), respectively; additionally, rats underwent sham surgery were treated with PBS as controls.

Results

MiR-146a was upregulated in BMMSCs, and BMMSCs derived exosomes post miR-mimic transfection. Then in SCI rats, BMMSCs exosomes elevated the Basso, Beattie, and Bresnahan (BBB) score and reduced hematoxylin&eosin-reflected spinal cord tissue injury. In addition, BMMSCs exosomes did not affect TUNEL positive cells rate while increased NeuN(+) cells/field in spinal cord tissue from SCI rats. As for inflammation, BMMSCs exosomes repressed pro-inflammatory cytokine expressions, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, in spinal cord tissue from SCI rats. Furthermore, miR-146a overexpressed BMMSCs exosomes presented with notably better effects regarding elevating BBB score in SCI rats and reducing tissue injury, neuron apoptosis, and inflammation while enhancing neuron viability in spinal cord tissue from SCI rats.

Conclusions

MiR-146a overexpressed BMMSCs exosomes enhance locomotor capacity and neuron viability while reducing neuron apoptosis and spinal cord tissue inflammation in SCI rats.

中文翻译：

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来自过表达骨髓间充质干细胞的 microRNA 146a 的外泌体可保护大鼠免受脊髓损伤

背景

本研究旨在探讨过表达骨髓间充质干细胞（BMMSC）外泌体的 microRNA 146a（miR-146a）对脊髓损伤（SCI）恢复的影响。

方法

分离大鼠 BMMSC，并用 miR-146a 模拟物 (miR-mimic) 和对照模拟物 (NC-mimic) 转染，然后分离其外泌体。然后，构建SCI大鼠模型，然后用磷酸盐缓冲液（PBS）、NC BMMSCs外泌体（从带有NC-mimic的BMMSCs培养基中分离）和miR-146a过表达的BMMSCs外泌体（从BMMSCs培养基中分离）处理。分别与 miR-mimic）；此外，用 PBS 处理接受假手术的大鼠作为对照。

结果

miR-146a 在 BMMSC 和miR 模拟转染后衍生的外泌体中上调。然后，在 SCI 大鼠中，BMMSC 外泌体提高了 Basso、Beattie 和 Bresnahan (BBB) 评分，并减少了苏木精和伊红反映的脊髓组织损伤。此外，BMMSCs外泌体不影响TUNEL阳性细胞率，但增加了SCI大鼠脊髓组织中的NeuN(+)细胞/视野。至于炎症，BMMSC 外泌体抑制 SCI 大鼠脊髓组织中促炎细胞因子的表达，包括白细胞介素 (IL)-1β、IL-6 和肿瘤坏死因子 (TNF)-α。此外，过表达 miR-146a 的 BMMSC 外泌体在提高 SCI 大鼠的 BBB 评分、减少组织损伤、神经元凋亡和炎症方面表现出明显更好的效果，同时增强 SCI 大鼠脊髓组织中的神经元活力。

结论

MiR-146a 过表达的 BMMSC 外泌体可增强 SCI 大鼠的运动能力和神经元活力，同时减少神经元凋亡和脊髓组织炎症。