Department of Neuroscience, University of Texas at Austin, Austin, TX, 78712, USA.
School of Pharmacy, University of Wyoming, Laramie, WY, 82072, USA.
J Neuroinflammation. 2022 Feb 28;19(1):60. doi: 10.1186/s12974-022-02395-0.
We review data showing that peripheral nerve injuries (PNIs) that involve the loss of a nerve segment are the most common type of traumatic injury to nervous systems. Segmental-loss PNIs have a poor prognosis compared to other injuries, especially when one or more mixed motor/sensory nerves are involved and are typically the major source of disability associated with extremities that have sustained other injuries. Relatively little progress has been made, since the treatment of segmental loss PNIs with cable autografts that are currently the gold standard for repair has slow and incomplete (often non-existent) functional recovery. Viable peripheral nerve allografts (PNAs) to repair segmental-loss PNIs have not been experimentally or clinically useful due to their immunological rejection, Wallerian degeneration (WD) of anucleate donor graft and distal host axons, and slow regeneration of host axons, leading to delayed re-innervation and producing atrophy or degeneration of distal target tissues. However, two significant advances have recently been made using viable PNAs to repair segmental-loss PNIs: (1) hydrogel release of Treg cells that reduce the immunological response and (2) PEG-fusion of donor PNAs that reduce the immune response, reduce and/or suppress much WD, immediately restore axonal conduction across the donor graft and re-innervate many target tissues, and restore much voluntary behavioral functions within weeks, sometimes to levels approaching that of uninjured nerves. We review the rather sparse cellular/biochemical data for rejection of conventional PNAs and their acceptance following Treg hydrogel and PEG-fusion of PNAs, as well as cellular and systemic data for their acceptance and remarkable behavioral recovery in the absence of tissue matching or immune suppression. We also review typical and atypical characteristics of PNAs compared with other types of tissue or organ allografts, problems and potential solutions for PNA use and storage, clinical implications and commercial availability of PNAs, and future possibilities for PNAs to repair segmental-loss PNIs.
我们回顾了数据，这些数据表明，涉及神经节段缺失的周围神经损伤（PNI）是神经系统最常见的创伤类型。与其他损伤相比，节段性缺失 PNI 的预后较差，尤其是当涉及一个或多个混合运动/感觉神经时，并且通常是与其他损伤相关的四肢残疾的主要来源。自目前修复的金标准电缆自体移植物治疗节段性 PNI 以来，进展相对较少，因为其功能恢复缓慢且不完全（通常不存在）。由于其免疫排斥、去神经供体移植物和远端宿主轴突的沃勒变性（WD）以及宿主轴突的缓慢再生，可行的周围神经同种异体移植物（PNAs）用于修复节段性 PNI 并没有在实验或临床上有用，导致延迟再神经支配并产生远端靶组织萎缩或变性。然而，最近使用可行的 PNA 修复节段性 PNI 取得了两项重大进展：（1）Treg 细胞的水凝胶释放可减少免疫反应，（2）PEG 融合供体 PNA 可减少免疫反应、减少和/或抑制大量 WD，立即恢复供体移植物中的轴突传导并重新支配许多靶组织，并在数周内恢复许多自主行为功能，有时接近未受伤神经的水平。我们回顾了关于传统 PNA 排斥及其在 Treg 水凝胶和 PNA PEG 融合后的接受情况的相当稀疏的细胞/生化数据，以及关于它们的接受和在没有组织匹配或免疫抑制的情况下显著行为恢复的细胞和系统数据。我们还回顾了 PNA 与其他类型的组织或器官同种异体移植物相比的典型和非典型特征、PNA 使用和储存的问题和潜在解决方案、PNA 的临床意义和商业可用性，以及 PNA 修复节段性 PNI 的未来可能性。
