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使用等离子体衍生外泌体处理的神经同种异体移植物增强节段性神经缺损后的功能恢复。

Enhancing Functional Recovery after Segmental Nerve Defect Using Nerve Allograft Treated with Plasma-Derived Exosome.

机构信息

From the Department of Orthopedics, Jinling Hospital, School of Medicine, Nanjing University.

Division of Plastic Surgery, Department of Surgery.

出版信息

Plast Reconstr Surg. 2023 Dec 1;152(6):1247-1258. doi: 10.1097/PRS.0000000000010389. Epub 2023 Mar 14.

Abstract

BACKGROUND

Nerve injuries can result in detrimental functional outcomes. Currently, autologous nerve graft offers the best outcome for segmental peripheral nerve injury. Allografts are alternatives, but do not have comparable results. This study evaluated whether plasma-derived exosome can improve nerve regeneration and functional recovery when combined with decellularized nerve allografts.

METHODS

The effect of exosomes on Schwann cell proliferation and migration were evaluated. A rat model of sciatic nerve repair was used to evaluate the effect on nerve regeneration and functional recovery. A fibrin sealant was used as the scaffold for exosome. Eighty-four Lewis rats were divided into autograft, allograft, and allograft with exosome groups. Gene expression of nerve regeneration factors was analyzed on postoperative day 7. At 12 and 16 weeks, rats were subjected to maximum isometric tetanic force and compound muscle action potential. Nerve specimens were then analyzed by means of histology and immunohistochemistry.

RESULTS

Exosomes were readily taken up by Schwann cells that resulted in improved Schwann cell viability and migration. The treated allograft group had functional recovery (compound muscle action potential, isometric tetanic force) comparable to that of the autograft group. Similar results were observed in gene expression analysis of nerve regenerating factors. Histologic analysis showed no statistically significant differences between treated allograft and autograft groups in terms of axonal density, fascicular area, and myelin sheath thickness.

CONCLUSIONS

Plasma-derived exosome treatment of decellularized nerve allograft may provide comparable clinical outcomes to that of an autograft. This can be a promising strategy in the future as an alternative for segmental peripheral nerve repair.

CLINICAL RELEVANCE STATEMENT

Off-the-shelf exosomes may improve recovery in nerve allografts.

摘要

背景

神经损伤可导致不良的功能结果。目前,自体神经移植为节段性周围神经损伤提供了最佳结果。同种异体移植物是替代品,但结果不可比。本研究评估了在脱细胞同种异体神经移植物中联合使用血浆衍生的外泌体是否可以改善神经再生和功能恢复。

方法

评估了外泌体对施万细胞增殖和迁移的影响。使用大鼠坐骨神经修复模型评估对神经再生和功能恢复的影响。纤维蛋白胶用作外泌体的支架。84 只 Lewis 大鼠分为自体移植物、同种异体移植物和同种异体移植物加外泌体组。术后第 7 天分析神经再生因子的基因表达。在 12 周和 16 周时,大鼠进行最大等长强直收缩和复合肌肉动作电位。然后通过组织学和免疫组织化学分析神经标本。

结果

外泌体很容易被施万细胞摄取,从而提高了施万细胞的活力和迁移能力。经处理的同种异体移植物组的功能恢复(复合肌肉动作电位、等长强直收缩力)与自体移植物组相当。神经再生因子的基因表达分析也观察到了类似的结果。组织学分析显示,在轴突密度、束状区和髓鞘厚度方面,经处理的同种异体移植物组与自体移植物组之间无统计学差异。

结论

脱细胞同种异体神经移植物的血浆衍生外泌体治疗可能提供与自体移植物相当的临床结果。这可能是未来作为节段性周围神经修复替代物的有前途的策略。

临床相关性声明

现成的外泌体可能会改善神经同种异体移植物的恢复。

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