Spinal cord injury (SCI) may lead to severe motor and sensory dysfunction, causing high mortality and disability rates. Adipose tissue-derived mesenchymal stem/stromal cells (ADSCs), especially hypoxia-pretreated ADSCs, represent an effective therapy for SCI by promoting the secretion of exosomes (Exos). Here, we investigated the therapeutic efficacy of exosomes secreted by ADSCs under hypoxia (HExos) and explored potential target molecules. We utilized nanoparticle tracking analysis, electron microscopy, qRT-PCR, and western blotting to analyze differences between HExos and Exos groups. The expression of long noncoding RNAs (lncRNAs) was examined by high-throughput sequencing. The therapeutic effects of different Exos treatments were compared in vitro and in an SCI model in vivo. The interaction between lncRNAs, microRNAs, and mRNA was examined by luciferase reporter experiments. We employed enzyme-linked immunosorbent assay and immunofluorescence to measure inflammatory factor expression and microglial polarization. The results showed that HExos was more effective than Exos for repairing SCI by suppressing inflammatory factor expression, promoting functional recovery, and shifting microglia from M1 to M2 polarization. High-throughput sequencing showed that LncGm37494 expression was significantly higher in HExos than Exos, and its upregulation promoted microglial M1/M2 polarization by inhibiting miR-130b-3p and promoting PPARγ expression, as shown by luciferase reporter experiments. Exos from lncGm37494 overexpressing ADSCs showed a similar therapeutic effect than HExos. The results indicated that HExos repair SCI by delivering lncGm37494, advising that lncGm3749 functions importantly in microenvironmental regulation and shows possibility for SCI treatments.

中文翻译：

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来自长非编码 RNA-Gm37494-ADSCs 的外泌体通过改变小胶质细胞 M1/M2 极化来修复脊髓损伤。

脊髓损伤 (SCI) 可能导致严重的运动和感觉功能障碍，导致高死亡率和残疾率。脂肪组织来源的间充质干/基质细胞 (ADSCs)，尤其是经过缺氧预处理的 ADSCs，通过促进外泌体 (Exos) 的分泌来代表 SCI 的有效疗法。在这里，我们研究了 ADSC 在缺氧 (HE​​xos) 下分泌的外泌体的治疗效果，并探索了潜在的靶分子。我们利用纳米粒子追踪分析、电子显微镜、qRT-PCR 和蛋白质印迹来分析 HExos 和 Exos 组之间的差异。通过高通量测序检查长非编码 RNA (lncRNA) 的表达。在体外和体内 SCI 模型中比较了不同 Exos 治疗的治疗效果。lncRNAs、microRNAs、通过荧光素酶报告实验检查mRNA。我们采用酶联免疫吸附测定和免疫荧光来测量炎症因子表达和小胶质细胞极化。结果表明，通过抑制炎症因子表达、促进功能恢复以及将小胶质细胞从 M1 极化转变为 M2 极化，HExos 比 Exos 更有效地修复 SCI。高通量测序显示 LncGm37494 在 HExos 中的表达明显高于 Exos，其上调通过抑制 miR-130b-3p 和促进 PPARγ 表达促进小胶质细胞 M1/M2 极化，如荧光素酶报告实验所示。来自过表达 ADSCs 的 lncGm37494 的 Exos 显示出与 HExos 相似的治疗效果。结果表明，HExos 通过递送 lncGm37494 修复 SCI，