Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
Neurosurgery. 2009 Oct;65(4 Suppl):A80-6. doi: 10.1227/01.NEU.0000335651.93926.2F.
The purpose of this review is to summarize the basic science literature related to chronic nerve injuries, and to then use this as the background to provide emerging insights into the promising role of cellular therapy for nerve injury repair.
The literature pertinent to the experimental and clinical aspects of chronic nerve injury was reviewed, as was emerging literature and our own recent experience in using cellular therapy to repair injured nerves.
Peripheral nerves have the potential to regenerate axons and reinnervate end organs. Yet, outcome after peripheral nerve injury, even after nerve repair, remains relatively poor. The single most important quantitative contributor to poor motor recovery is chronic denervation of the distal nerve. Chronic denervation is common because of the often extensive injury zone that prevents any axonal outgrowth or (even if outgrowth occurs) the relatively slow rate of regeneration. As a consequence, the distal nerve remains chronically devoid of regrowing axons. In turn, prolonged denervation of Schwann cells (SCs) seems to be the critical factor that makes them unreceptive for axonal regeneration. Regenerative success was demonstrated when denervated SCs were replaced with healthy SCs cultured from a secondary nerve. This cell-replacement strategy is, however, limited in the clinical setting by the inability to obtain sufficient numbers of cells and the requirement for sacrifice of additional nerve tissue. We, along with several other groups, have therefore begun investigating stem cell therapies to improve the regenerative environment.
There are several avenues of stem cell-based approaches to peripheral nerve repair. One of these, skin-derived precursor cells, are easily accessible, autologous adult stem cells that can survive and myelinate in the peripheral nerve environment and become SC-like in their apparent differentiation.
本篇综述的目的在于总结与慢性神经损伤相关的基础科学文献，在此基础上探讨细胞疗法在神经损伤修复方面的应用前景。
我们对慢性神经损伤的实验和临床相关文献进行了综述，并对新兴文献和我们使用细胞疗法修复受损神经的最新经验进行了探讨。
周围神经具有再生轴突和重新支配终末器官的潜力。然而，周围神经损伤后的结果，即使在神经修复后，仍然相对较差。导致运动功能恢复不良的最重要的单一因素是远端神经的慢性失神经支配。慢性失神经支配很常见，因为损伤区域通常很广泛，这会阻止任何轴突生长，或者即使发生了生长，再生速度也相对较慢。因此，远端神经长期缺乏再生的轴突。反过来，施万细胞（SCs）的长期失神经支配似乎是使其对轴突再生不敏感的关键因素。当用从次级神经培养的健康SCs 替代失神经支配的SCs 时，已经证明了再生的成功。然而，这种细胞替代策略在临床环境中受到限制，因为无法获得足够数量的细胞，并且需要牺牲额外的神经组织。因此，我们和其他几个研究小组一起，开始研究干细胞疗法以改善再生环境。
有几种基于干细胞的方法可用于周围神经修复。其中一种方法是皮肤衍生前体细胞，它是一种易于获得的、自体成体干细胞，可在周围神经环境中存活并髓鞘化，并在其明显分化中表现出类似施万细胞的特征。
