中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (4): 721-727.doi: 10.4103/1673-5374.322445

• 综述:周围神经损伤修复保护与再生 • 上一篇    下一篇

周围神经异体移植物的功能和免疫特性

  

  • 出版日期:2022-04-15 发布日期:2021-10-16

Functional and immunological peculiarities of peripheral nerve allografts

Kelly C.S. Roballo1, Jason P. Gigley2, Tyler A. Smith3, George D. Bittner4, Jared S. Bushman1, *#br#   

  1. 1School of Pharmacy, University of Wyoming, Laramie, WY, USA; 2Department of Molecular Biology, University of Wyoming, Laramie, WY, USA; 3Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA; 4Department of Neuroscience, University of Texas at Austin, Austin, TX, USA
  • Online:2022-04-15 Published:2021-10-16
  • Contact: Jared S. Bushman, PhD, jbushman@uwyo.edu.
  • Supported by:
    This work was supported by University of Wyoming Startup Funds, United States Department of Defense, grant No. W81XWH-17-1-0402, the University of Wyoming Sensory Biology COBRE under National Institutes of Health (NIH), award number 5P20GM121310-02, the National Institute of General Medical Sciences of the NIH under Award Number P20GM103432 (to JSB). This work was also supported by grants from the Lone Star Paralysis Foundation, NIH R01NS081063, and Department of Defense award W81XWH-19-2-0054 to GDB. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US Department of Defense, NIH, University of Texas, or the University of Wyoming. 

摘要: Neural Regen Res: 周围神经移植物通过轴突融合和轴突再生桥接周围神经缺损  
    最常见的神经功能障碍是由节段性缺损组成的创伤性周围神经损伤。治疗节段性缺损的理想桥接导管是自体神经,其感觉运动成分、轴突数量和轴突组织与损伤神经相似。如果活的周围神经移植物没有免疫原性,有几种方法比自体感觉神经移植物更有效。首先,从供体尸体中回收和储存的周围神经移植物不会引起宿主发病。第二,周围神经移植物可以与缺损部位进行感觉运动匹配,产生比单纯感觉移植物更好的运动轴突再生。这种匹配神经比单纯感觉神经更能促进神经再生的原因尚不完全清楚,但运动相关雪旺细胞似乎与传感器相关雪旺细胞有本质的区别,并能促进运动轴突的高级再生和寻路。第三,周围神经移植物的直径、长度、分支结构和分支模式在解剖学上是匹配的,而这些往往是成功神经再生的重要因素。解剖结构的不匹配增加了下一级再生、纤维化、神经瘤、随机靶点神经再支配和较差的功能。轴突数目和密度与缺损的匹配可能也是最大化节段性缺损轴突融合的关键考虑因素。第四,可以采集周围神经移植物以匹配复杂的神经结构,例如分支点。没有其他策略可以修复包含分支点的节段性周围神经缺陷。
    来自美国怀俄明大学的Jared S. Bushman团队认为,经免疫抑制治疗的周围神经移植物恢复良好,无排斥反应。在一个特别复杂的情况下,一名内侧尺骨严重节段性缺损的患者接受了自体腓肠肌移植和内侧尺骨神经同种异体移植的联合治疗。植入前几天开始使用环孢素A、硫唑嘌呤和强的松进行免疫抑制,并持续12个月。术后33个月,患者的尺侧和正中肌的神经支配良好。另一例患者在远端指神经修复手术前几天和术后至少6个月接受免疫抑制治疗,结果相似。应用1%美蓝聚乙二醇融合治疗指神经单侧切断伤,在伤后24小时成功修复。也就是说,聚乙二醇融合快速恢复了单一切断的人指神经的感觉。虽然众所周知,中枢神经系统具有一定程度的免疫特权,但越来越多的证据表明,外周神经系统在免疫上也是特殊的。这些特点在异基因周围神经移植后尤其明显,宿主的免疫反应比其他移植组织更为缓慢,也不那么严重。这些差异可能是由于周围神经移植物作为宿主轴突再生的临时支架的功能差异,以及与许多其他移植组织的内在免疫差异。进一步研究这些特性的机制将有助于周围神经再生和移植领域的研究。 
文章在《中国神经再生研究(英文版)》杂志2022年4 月 4 期发表。

https://orcid.org/0000-0002-0128-5445 (Jared S. Bushman) 

Abstract: This review addresses the accumulating evidence that live (not decellularized) allogeneic peripheral nerves are functionally and immunologically peculiar in comparison with many other transplanted allogeneic tissues. This is relevant because live peripheral nerve allografts are very effective at promoting recovery after segmental peripheral nerve injury via axonal regeneration and axon fusion. Understanding the immunological peculiarities of peripheral nerve allografts may also be of interest to the field of transplantation in general. Three topics are addressed: The first discusses peripheral nerve injury and the potential utility of peripheral nerve allografts for bridging segmental peripheral nerve defects via axon fusion and axon regeneration. The second reviews evidence that peripheral nerve allografts elicit a more gradual and less severe host immune response allowing for prolonged survival and function of allogeneic peripheral nerve cells and structures. Lastly, potential mechanisms that may account for the immunological differences of peripheral nerve allografts are discussed. 

Key words: allograft, animal model, immunology, neuroimmunology, peripheral nerve injury, regeneration, repair, tissue regeneration, tissue transplantation, transplant