■面神经有可能在损伤后再生,但是这个过程通常是具有挑战性和缓慢的。雪旺氏细胞(SCs)在此过程中至关重要。骨髓间充质干细胞(BMSC)来源的外泌体通过旁分泌作用促进组织修复,与低氧预处理增强其效果。这项研究的主要目的是确定缺氧预处理的BMSC衍生的外泌体(Hypo-Exos)是否对面神经修复/再生具有更大的治疗作用,并揭示其机制。
■CCK-8,EdU,Transwell,和ELISA测定用于评估Hypo-Exos在SCs中的功能。组织学分析和Vibrisae运动(VM)恢复用于评估Hypo-Exos在大鼠模型中的治疗效果。circRNA阵列用于鉴定正常含氧量预处理的BMSC衍生的外泌体(Nor-Exos)和Hypo-Exos之间显着差异表达的外泌体circRNA。miRDB,TargetScan,双荧光素酶测定,qRT-PCR和WB用于预测和鉴定潜在的外泌体cirRNA_Nkd2-互补miRNAs及其靶基因。通过细胞和动物实验评估了外泌体circRNA_Nkd2在面神经修复/再生中的功能。
■这项研究证实,Hypo-Exos更有效地促进SCs增殖,迁移,和旁分泌功能,与Nor-Exos相比,在面神经损伤(FNI)后加速面神经修复。此外,circRNA分析鉴定了与Nor-Exos相比,Hypo-Exos中circRNA_Nkd2的显着富集。外来体circRNA_Nkd2通过海绵rno-miR-214-3p正向调节介质复合物亚基19(MED19)的表达。
■我们的结果证明了Hypo-Exos增强SCs增殖的机制,迁移,通过circRNA_Nkd2/miR-214-3p/Med19轴,FNI后的旁分泌功能和面神经修复和再生。低氧预处理是优化FNI中BMSC来源的外泌体治疗作用的有效且有前途的方法。
UNASSIGNED: Facial nerves have the potential for regeneration following injury, but this process is often challenging and slow. Schwann cells (SCs) are pivotal in this process. Bone mesenchymal stem cells (BMSC)-derived exosomes promote tissue repair through paracrine action, with hypoxic preconditioning enhancing their effects. The main purpose of this study was to determine whether hypoxia-preconditioned BMSC-derived exosomes (Hypo-Exos) exhibit a greater therapeutic effect on facial nerve repair/regeneration and reveal the mechanism.
UNASSIGNED: CCK-8, EdU, Transwell, and ELISA assays were used to evaluate the functions of Hypo-Exos in SCs. Histological analysis and Vibrissae Movements (VMs) recovery were used to evaluate the therapeutic effects of Hypo-Exos in rat model. circRNA array was used to identify the significantly differentially expressed exosomal circRNAs between normoxia-preconditioned BMSC-derived exosomes (Nor-Exos) and Hypo-Exos. miRDB, TargetScan, double luciferase assay, qRT-PCR and WB were used to predict and identify potential exosomal cirRNA_Nkd2-complementary miRNAs and its target gene. The function of exosomal circRNA_Nkd2 in facial nerve repair/regeneration was evaluated by cell and animal experiments.
UNASSIGNED: This study confirmed that Hypo-Exos more effectively promote SCs proliferation, migration, and paracrine function, accelerating facial nerve repair following facial nerve injury (FNI) compared with Nor-Exos. Furthermore, circRNA analysis identified significant enrichment of circRNA_Nkd2 in Hypo-Exos compared with Nor-Exos. Exosomal circRNA_Nkd2 positively regulates mediator complex subunit 19 (MED19) expression by sponging rno-miR-214-3p.
UNASSIGNED: Our results demonstrated a mechanism by which Hypo-Exos enhanced SCs proliferation, migration, and paracrine function and facial nerve repair and regeneration following FNI through the circRNA_Nkd2/miR-214-3p/Med19 axis. Hypoxic preconditioning is an effective and promising method for optimizing the therapeutic action of BMSC-derived exosomes in FNI.