Goldman Steven A, Windrem Martha S
Division of Cell and Gene Therapy, Department of Neurology, University of Rochester Medical Center, 601 Elmwood Avenue, PO Box 645, Rochester, NY 14642, USA.
Philos Trans R Soc Lond B Biol Sci. 2006 Sep 29;361(1473):1463-75. doi: 10.1098/rstb.2006.1886.
Diseases of the brain and spinal cord represent especially daunting challenges for cell-based strategies of repair, given the multiplicity of cell types within the adult central nervous system, and the precision with which they must interact in both space and time. Nonetheless, a number of diseases are especially appropriate for cell-based therapy, in particular those in which single phenotypes are lost, and in which the re-establishment of vectorially specific connections is not entirely requisite for therapeutic benefit. We review here a set of potential therapeutic indications that meet these criteria as potentially benefiting from the transplantation of neural stem and progenitor cells. These include: (i) transplantation of phenotypically restricted neuronal progenitor cells into diseases of a single neuronal phenotype, such as Parkinson's disease; (ii) implantation of mixed progenitor pools into diseases characterized by the loss of a limited number of discrete phenotypes, such as spinal cord injury and the motor neuronopathies; (iii) transplantation of glial and nominally oligodendrocytic progenitor cells as a means of treating disorders of myelin; and (iv) transplantation of neural stem cells as a means of treating lysosomal storage disorders and other diseases of enzymatic deficiency. Among the diseases potentially approachable by these strategies, the myelin disorders, including the paediatric leucodystrophies as well as adult traumatic and inflammatory demyelinations, may present the most compelling targets for cell-based neurological therapy.
鉴于成体中枢神经系统中细胞类型的多样性，以及它们在空间和时间上相互作用所需的精确性，脑和脊髓疾病对于基于细胞的修复策略而言是尤其艰巨的挑战。尽管如此，一些疾病特别适合基于细胞的治疗，尤其是那些单一表型丧失，且重新建立矢量特异性连接对于治疗益处并非完全必要的疾病。我们在此综述了一系列符合这些标准、可能受益于神经干细胞和祖细胞移植的潜在治疗适应症。这些包括：（i）将表型受限的神经元祖细胞移植到单一神经元表型的疾病中，如帕金森病；（ii）将混合祖细胞群植入以有限数量离散表型丧失为特征的疾病中，如脊髓损伤和运动神经元病；（iii）移植神经胶质和名义上的少突胶质祖细胞作为治疗髓鞘疾病的一种手段；以及（iv）移植神经干细胞作为治疗溶酶体贮积症和其他酶缺乏症的一种手段。在这些策略可能适用的疾病中，髓鞘疾病，包括小儿脑白质营养不良以及成人创伤性和炎性脱髓鞘疾病，可能是基于细胞的神经治疗最具吸引力的靶点。
