Miller Robert H, Bai Lianhua
Center for Translational Neuroscience, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Regen Med. 2007 Sep;2(5):817-29. doi: 10.2217/17460751.2.5.817.
Myelination is critical for the normal functioning of the vertebrate nervous system. In the CNS, myelin is produced by oligodendrocytes, and the loss of oligodendrocytes and myelin results in severe functional impairment. Although spontaneous remyelination occurs in chronic demyelinating diseases such as multiple sclerosis, the repair process eventually fails, often resulting in long-term disability. Two distinct general approaches can be considered to promote myelin repair. In one the target is stimulation of the endogenous myelin repair process through delivery of growth factors, and in the second the target is augmentation of the repair process through the delivery of exogenous cells with myelination potential. In both cases, effective treatment of diseases such as multiple sclerosis requires modulation of the immune system, since demyelination is associated with specific immunological activation. Recent studies have shown that some populations of stem cells, including mesenchymal stem cells, have the capacity of promoting endogenous myelin repair and modulating the immune response, prompting an assessment of their use as therapy in demyelinating diseases such as MS. Other types of demyelinating disorders, such as the leukodystrophies, may require multiple repair strategies including both replacement of dysfunctional cells and delivery or supplementation of growth factors, immune modulators or metabolic enzymes. Here we discuss the use of stem cells for the treatment of demyelinating diseases. While the current number of stem cell-based clinical trials for demyelinating diseases is limited, this is likely to increase significantly in the next few years, and a clear understanding of the applicability, limitations and underlying mechanisms mediating stem cell repair is critical.
髓鞘形成对于脊椎动物神经系统的正常功能至关重要。在中枢神经系统中，髓鞘由少突胶质细胞产生，少突胶质细胞和髓鞘的丧失会导致严重的功能障碍。尽管在诸如多发性硬化症等慢性脱髓鞘疾病中会发生自发的髓鞘再生，但修复过程最终会失败，常常导致长期残疾。可以考虑两种不同的总体方法来促进髓鞘修复。一种方法的目标是通过递送生长因子来刺激内源性髓鞘修复过程，另一种方法的目标是通过递送具有髓鞘形成潜力的外源性细胞来增强修复过程。在这两种情况下，有效治疗诸如多发性硬化症等疾病都需要调节免疫系统，因为脱髓鞘与特定的免疫激活相关。最近的研究表明，一些干细胞群体，包括间充质干细胞，具有促进内源性髓鞘修复和调节免疫反应的能力，这促使人们评估它们在诸如多发性硬化症等脱髓鞘疾病治疗中的应用。其他类型的脱髓鞘疾病，如脑白质营养不良，可能需要多种修复策略，包括替换功能失调的细胞以及递送或补充生长因子、免疫调节剂或代谢酶。在此我们讨论干细胞在脱髓鞘疾病治疗中的应用。虽然目前基于干细胞的脱髓鞘疾病临床试验数量有限，但在未来几年这一数量可能会显著增加，因此清楚了解干细胞修复的适用性、局限性及潜在机制至关重要。
