Glaser Tamara, Schmandt Tanja, Brüstle Oliver
Institute of Reconstructive Neurobiology, Life and Brain Center, University of Bonn and Hertie Foundation, Bonn, Germany.
J Neurol Sci. 2008 Feb 15;265(1-2):47-58. doi: 10.1016/j.jns.2007.09.018. Epub 2007 Oct 26.
Recent progress in embryonic and adult stem cell research has opened new perspectives for generating large numbers of different neural cell types in vitro and using them for nervous system repair. Several lines of arguments suggest that myelin diseases represent particularly attractive targets for cell-based therapies. First, in contrast to neuronal cell replacement, a single and uniform cell type, the oligodendrocyte progenitor, suffices for therapeutic remyelination in all areas of the CNS, with no need for complex circuit integration. Second, there is an increasing understanding of the mechanisms regulating the recruitment of stem and progenitor cells into CNS lesions. Third, stem cells represent excellent vehicles for cell-mediated gene transfer, enabling novel approaches, which combine classic cell replacement with the delivery of therapeutic factors. Among the various donor sources, embryonic stem (ES) cells stand out as a population featuring pluripotency, unlimited self-renewal and amenability to gene targeting. Here we discuss the advantages, challenges and perspectives of bringing this unique cell type closer to a clinical application for treating myelin diseases and other neurological disorders.
胚胎干细胞和成体干细胞研究的最新进展为体外大量生成不同类型神经细胞并将其用于神经系统修复开辟了新前景。有几条论据表明,髓鞘疾病是基于细胞疗法特别有吸引力的靶点。首先,与神经元细胞替代不同,一种单一且统一的细胞类型,即少突胶质细胞前体细胞,就足以在中枢神经系统的所有区域进行治疗性髓鞘再生,无需复杂的神经回路整合。其次,人们对调节干细胞和前体细胞募集到中枢神经系统损伤部位的机制的理解日益加深。第三,干细胞是细胞介导基因转移的理想载体,能够实现将经典细胞替代与治疗因子递送相结合的新方法。在各种供体来源中,胚胎干细胞作为具有多能性、无限自我更新能力且易于进行基因靶向操作的细胞群体脱颖而出。在此,我们讨论将这种独特细胞类型更接近用于治疗髓鞘疾病和其他神经系统疾病临床应用的优势、挑战和前景。