原标题：【敲黑板】外泌体新发现 — 骨髓间充质干细胞来源外泌体有望促进脊髓损伤修复
脊髓损伤（Spinal cord injury，SCI）是一种危及生命的创伤性损伤，常伴有截瘫、神经系统并发症和预期寿命缩短。原发创伤事件发生后，一系列继发性损伤事件开始发生，包括缺血、出血、血脊髓屏障（Blood-spinal cord barrier，BSCB）破裂、水肿、神经炎症和氧化应激。这些过程最终会加速神经元丧失和轴突变性。其中，BSCB的破裂和神经炎症是SCI发病的关键事件，使脊髓的正常功能恢复更加困难。已有研究表明，间充质干细胞(Mesenchymal stem cell, MSC)移植是一种很有前途的治疗脊髓损伤的策略，但免疫排斥反应限制了其应用。骨髓间充质干细胞（Bone marrow mesenchymal stem cell，BMSC）的治疗效果主要取决于其可溶性旁分泌因子的释放，其中外泌体（EXO）对于旁分泌作用是必不可少的。骨髓间充质干细胞来源的外泌体（BMSC-EXOs）可以在细胞移植中替代BMSCs。然而，潜在的机制仍不清楚。近日，有研究人员报道了BMSC-EXOs可能通过抑制细胞焦亡和改善血脊髓屏障完整性来保护脊髓受损。相关研究结果发表在Neural Regeneration Research上。
为评估BMSC-EXOs治疗脊髓损伤效果，研究人员首先构建了脊髓损伤大鼠模型。在脊髓损伤30分钟和1天后，经尾静脉给药200μL外泌体(200μg/mL;大约1×106个骨髓间充质干细胞)。结果发现BMSC-EXOs治疗可显著减少神经细胞死亡，改善髓鞘排列和减少髓鞘丢失，增加血管壁周细胞/内皮细胞覆盖，减少血脊髓屏障渗漏，减少 半胱天冬酶 1表达，抑制白细胞介素1β释放，加速脊髓损伤大鼠运动功能恢复。细胞培养实验用干扰素-γ和肿瘤坏死因子-α处理周细胞。用Lipofectamine 3000将脂多糖导入细胞，与三磷酸腺苷共孵育，模拟体外损伤。BMSC-EXOs预处理8小时可显著降低周细胞焦亡，提高周细胞存活率。综上，该研究结果提示BMSC-EXOs可能通过抑制细胞焦亡和改善血脊髓屏障完整性来保护神经元存活和促进神经纤维的延伸，最终改善脊髓损伤大鼠的运动功能。
Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis.
Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 μL exosomes via the tail vein (200 μg/mL; approximately 1 × 106 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1β release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury.
编辑：胡肖希
美编：王 乐
审核：辛嘉平
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本文内容转载至上海市脐带血造血干细胞库，仅为学术分享，如涉侵权请联系删除
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