Schwann cell–derived exosomes communicate with dorsal root ganglia (DRG) neurons. The current study investigated the therapeutic effect of exosomes derived from healthy Schwann cells (SC-Exos) on diabetic peripheral neuropathy (DPN). We found that intravenous administration of SC-Exos to type 2 diabetic db/db mice with peripheral neuropathy remarkably ameliorated DPN by improving sciatic nerve conduction velocity and increasing thermal and mechanical sensitivity. These functional improvements were associated with the augmentation of epidermal nerve fibers and remyelination of sciatic nerves. Quantitative RT-PCR and Western blot analysis of sciatic nerve tissues showed that SC-Exo treatment reversed diabetes-reduced mature form of miRNA (miR)-21, -27a, and -146a and diabetes-increased semaphorin 6A (SEMA6A); Ras homolog gene family, member A (RhoA); phosphatase and tensin homolog (PTEN); and nuclear factor-κB (NF-κB). In vitro data showed that SC-Exos promoted neurite outgrowth of diabetic DRG neurons and migration of Schwann cells challenged by high glucose. Collectively, these novel data provide evidence that SC-Exos have a therapeutic effect on DPN in mice and suggest that SC-Exo modulation of miRs contributes to this therapy.

中文翻译：

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源自雪旺氏细胞的外泌体可改善 II 型糖尿病小鼠的周围神经病变

雪旺细胞衍生的外泌体与背根神经节 (DRG) 神经元通信。目前的研究调查了源自健康雪旺细胞（SC-Exos）的外泌体对糖尿病周围神经病变（DPN）的治疗效果。我们发现，对患有周围神经病变的 2 型糖尿病 db/db 小鼠静脉注射 SC-Exos 可通过改善坐骨神经传导速度和增加热和机械敏感性显着改善 DPN。这些功能改善与表皮神经纤维的增加和坐骨神经的髓鞘再生有关。坐骨神经组织的定量 RT-PCR 和蛋白质印迹分析表明，SC-Exo 治疗逆转了糖尿病减少的成熟形式的 miRNA (miR)-21、-27a 和 -146a 和糖尿病增加的信号素 6A (SEMA6A)；Ras同源基因家族，成员A（RhoA）；磷酸酶和张力蛋白同源物（PTEN）；和核因子-κB (NF-κB)。体外数据表明，SC-Exos 促进了糖尿病 DRG 神经元的神经突生长和高糖挑战的雪旺氏细胞的迁移。总的来说，这些新数据提供了 SC-Exos 对小鼠 DPN 具有治疗作用的证据，并表明 SC-Exo 对 miRs 的调节有助于这种治疗。