PDF(Pubmed)
Abstract：
With a steadily aging population there is an increasing prevalence of neurological disorders. Given the lack of effective treatment strategies and a limited ability for the central nervous system (CNS) to regenerate endogenously, there is a critical need to better understand exogenous strategies for nervous system repair. Stem cell therapy offers a promising approach to promote the repair of neurologic tissue and function, however studies to date have been limited by various factors including challenges in harvesting donor cells from the CNS, ethical concerns regarding use of embryonic or fetal tissue, tumorigenic potential of induced pluripotent stem cells, and immune-mediated rejection of non-autologous cell sources. Here we review and propose two alternative sources of autologous cells derived from the peripheral nervous system (PNS) for CNS repair: enteric neuronal stem cells (ENSCs) and neural crest-derived Schwann cells found in subcutaneous adipose tissue (termed SAT-NSCs). ENSCs can be successfully isolated from the postnatal enteric nervous system, propagated in vitro, and transplanted successfully into models of CNS injury via both direct intracerebral injection and systemic tail vein injection. Similarly, SAT-NSCs can be readily isolated from both human and mouse adipose tissue and, although not yet utilized in models of CNS injury, have successfully been transplanted and restored function in models of colonic aganglionosis and gastroparesis. These unique sources of PNS-derived autologous cells offer an exciting option for stem cell therapies for the CNS as they have proven neurogenic potential and eliminate concerns around tumorigenic risk, ethical considerations, and immune-mediated rejection.
摘要：
随着人口的稳定老龄化，神经系统疾病的患病率越来越高。鉴于缺乏有效的治疗策略和中枢神经系统（CNS）内源性再生的能力有限，我们迫切需要更好地理解神经系统修复的外源性策略。干细胞疗法为促进神经组织和功能的修复提供了一种有希望的方法，然而，迄今为止的研究受到各种因素的限制，包括从中枢神经系统收获供体细胞的挑战，关于使用胚胎或胎儿组织的伦理问题，诱导多能干细胞的致瘤潜能，和免疫介导的非自体细胞来源的排斥反应。在这里，我们回顾并提出了来自周围神经系统（PNS）的自体细胞的两种替代来源，用于中枢神经系统修复：肠神经元干细胞（ENSC）和皮下脂肪组织中发现的神经c衍生的雪旺细胞（称为SAT-NSCs）。ENSC可以从出生后肠神经系统中成功分离，在体外繁殖，并通过直接脑内注射和全身尾静脉注射成功移植到中枢神经系统损伤模型中。同样，SAT-NSC可以很容易地从人和小鼠的脂肪组织中分离，虽然尚未用于中枢神经系统损伤模型，已成功移植并恢复结肠神经节病和胃轻瘫模型的功能。这些独特来源的PNS衍生的自体细胞为中枢神经系统的干细胞治疗提供了令人兴奋的选择，因为它们已经证明了神经源性潜力，并消除了对肿瘤发生风险的担忧。伦理考虑，和免疫介导的排斥反应。
