McKenzie Ian A, Biernaskie Jeff, Toma Jean G, Midha Rajiv, Miller Freda D
Department of Developmental Biology, Hospital For Sick Children Research Institute, Toronto, Ontario, Canada M5G 1X8.
J Neurosci. 2006 Jun 14;26(24):6651-60. doi: 10.1523/JNEUROSCI.1007-06.2006.
Although neural stem cells hold considerable promise for treatment of the injured or degenerating nervous system, their current human sources are embryonic stem cells and fetally derived neural tissue. Here, we asked whether rodent and human skin-derived precursors (SKPs), neural crest-related precursors found in neonatal dermis, represent a source of functional, myelinating Schwann cells. Specifically, cultured SKPs responded to neural crest cues such as neuregulins to generate Schwann cells, and these Schwann cells proliferated and induced myelin proteins when in contact with sensory neuron axons in culture. Similar results were obtained in vivo; 6 weeks after transplantation of naive SKPs or SKP-derived Schwann cells into the injured peripheral nerve of wild-type or shiverer mutant mice (which are genetically deficient in myelin basic protein), the majority of SKP-derived cells had associated with and myelinated axons. Naive rodent or human SKPs also generated Schwann cells that myelinated CNS axons when transplanted into the dysmyelinated brain of neonatal shiverer mice. Thus, neonatal SKPs generate functional neural progeny in response to appropriate neural crest cues and, in so doing, provide a highly accessible source of myelinating cells for treatment of nervous system injury, congenital leukodystrophies, and dysmyelinating disorders.
尽管神经干细胞在治疗受损或退化的神经系统方面具有巨大潜力，但其目前的人类来源是胚胎干细胞和胎儿来源的神经组织。在此，我们探讨了啮齿动物和人类皮肤衍生前体细胞（SKPs），即在新生儿真皮中发现的与神经嵴相关的前体细胞，是否可作为功能性髓鞘形成雪旺细胞的来源。具体而言，培养的SKPs对神经调节蛋白等神经嵴信号作出反应，从而生成雪旺细胞，并且这些雪旺细胞在与培养中的感觉神经元轴突接触时会增殖并诱导髓鞘蛋白的产生。在体内也获得了类似结果；将未经处理的SKPs或SKP衍生的雪旺细胞移植到野生型或颤抖突变小鼠（其髓鞘碱性蛋白存在基因缺陷）的受损周围神经中6周后，大多数SKP衍生细胞与轴突相关并形成髓鞘。将未经处理的啮齿动物或人类SKPs移植到新生颤抖小鼠的脱髓鞘脑中时，它们也会产生能使中枢神经系统轴突形成髓鞘的雪旺细胞。因此，新生儿SKPs在对适当的神经嵴信号作出反应时会产生功能性神经后代，这样一来，就为治疗神经系统损伤、先天性脑白质营养不良和脱髓鞘疾病提供了一种极易获取的髓鞘形成细胞来源。
