中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (5): 854-861.doi: 10.4103/1673-5374.232481

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

脂肪来源干细胞负载纤维蛋白导管修复坐骨神经损伤

  

  • 收稿日期:2018-03-16 出版日期:2018-05-15 发布日期:2018-05-15
  • 基金资助:

    德国慕尼黑大学医学基金

Validation of a novel animal model for sciatic nerve repair with an adipose derived stem cell loaded fibrin conduit

Maximilian M. Saller1, Rosa-Eva Huettl2, Julius M. Mayer1, 3, Annette Feuchtinger4, Christian Krug3, 5, Thomas Holzbach3, 5, Elias Volkmer1, 3   

  1. 1 Experimental Surgery and Regenerative Medicine (ExperiMed), Department of General, Trauma and Reconstructive Surgery,Ludwig-Maximilians-University (LMU), Munich, Germany
    2 Max-Planck-Institute of Psychiatry, Department of Stress Neurobiology and Neurogenetics, Munich, Germany
    3 Department of Hand-, Plastic- and Aesthetic Surgery, Ludwig-Maximilians-University (LMU), Munich, Germany
    4 Research Unit Analytical Pathology, Munich, Helmholtz Zentrum Muenchen-German Research Center for Environmental Health (GmbH),Neuherberg, Germany
    5 Department of Hand and Plastic Surgery, Spital Thurgau AG, Frauenfeld, Switzerland
  • Received:2018-03-16 Online:2018-05-15 Published:2018-05-15
  • Contact: Elias Volkmer, M.D.,elias_volkmer@hotmail.com
  • Supported by:

    This study was financially supported by the Faculty of Medicine, LMU (to TH and MMS; FöFole, Project 843 and 955).

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摘要：

尽管周围神经具有再生能力，但严重的神经元损伤对神经肌肉环路功能的恢复造成巨大障碍。自体神经移植促进了神经连接的重建，但同时也存在供体神经来源有限、供区损伤及再生时需要跨过两个吻合口等缺点。实验建立了大鼠模型，以测试脂肪间充质干细胞移植促进周围神经再生的作用。为了模仿自体神经移植物与受损神经的不精确对齐，实验切下20mm长的坐骨神经，并反转缝合回原处。将负载自体未分化脂肪来源干细胞的纤维蛋白凝胶导管应用在接合部位周围并与自体神经移植进行比较。术后16周评价坐骨神经功能后，测定腓肠肌重量以及再生轴突的形态参数（轴突髓鞘的g-ratio值、轴突密度和直径）。有趣的是，与自体神经移植相比，负载未分化的脂肪来源干细胞的导管可显著促进坐骨神经再髓鞘化、轴突向内生长和功能的恢复。由于纤维蛋白和脂肪来源干细胞已被批准用于临床，因而建议脂肪来源干细胞负载的纤维蛋白导管有潜力用于坐骨神经损伤的修复。

orcid:0000-0001-6888-5341(Elias Volkmer)

关键词: 神经缺损, 纤维蛋白导管, 自体神经移植, 周围神经再生, 脂肪干/祖细胞, 坐骨神经功能指数, 坐骨神经, 再支配, 轴突导向, 外周神经环路

Abstract:

Despite the regenerative capabilities of peripheral nerves, severe injuries or neuronal trauma of critical size impose immense hurdles for proper restoration of neuro-muscular circuitry. Autologous nerve grafts improve re-establishment of connectivity, but also comprise substantial donor site morbidity. We developed a rat model which allows the testing of different cell applications, i.e., mesenchymal stem cells, to improve nerve regeneration in vivo. To mimic inaccurate alignment of autologous nerve grafts with the injured nerve, a 20 mm portion of the sciatic nerve was excised, and sutured back in place in reversed direction.To validate the feasibility of our novel model, a fibrin gel conduit containing autologous undifferentiated adipose-derived stem cells was applied around the coaptation sites and compared to autologous nerve grafts. After evaluating sciatic nerve function for 16 weeks postoperatively, animals were sacrificed, and gastrocnemius muscle weight was determined along with morphological parameters (g-ratio, axon density & diameter) of regenerating axons. Interestingly, the addition of undifferentiated adipose-derived stem cells resulted in a significantly improved re-myelination, axon ingrowth and functional outcome, when compared to animals without a cell seeded conduit. The presented model thus displays several intriguing features: it imitates a certain mismatch in size, distribution and orientation of axons within the nerve coaptation site. The fibrin conduit itself allows for an easy application of cells and, as a true critical-size defect model, any observed improvement relates directly to the performed intervention. Since fibrin and adipose-derived stem cells have been approved for human applications, the technique can theoretically be performed on humans. Thus, we suggest that the model is a powerful tool to investigate cell mediated assistance of peripheral nerve regeneration.

Key words: critical-size nerve defect, fibrin conduit, autologous nerve transplant, peripheral nerve regeneration, adipose-derived stem/progenitor cells, sciatic function index, sciatic nerve, re-innervation, axon guidance, peripheral circuitry