Snyder E Y, Macklis J D
Harvard Medical School, Children's Hospital, Boston, MA, USA.
Clin Neurosci. 1995;3(5):310-6.
Multipotent neural progenitors or stem cells (or cells which mimic their behavior) are capable of differentiating along multiple central nervous system (CNS) cell-type lineages, neuronal and glial. They can engraft as integral members of normal structures throughout the host CNS without disturbing other neurobiological processes. By exploiting their basic biologic properties, these cells may be able to disseminate therapeutic gene products in a sustained, direct fashion throughout the CNS. In addition, they may replace dysfunctional neurons and glia in both a site-specific and global manner. They may play a therapeutic role in neurodegenerative conditions that occur both during development and in the mature brain. The ability of neural stem cells to respond to neurogenic cues not only when they occur during their normal developmental expression but even when induced or "reactivated" at later stages following injury, may entrance their utility in reconstituting damaged CNS regions. Thus, these vehicles may overcome many of the limitations of viral and non-neural cellular vectors, as well as pharmacologic and genetic interventions. The feasibility of this broadly applicable neural stem cell-based strategy has been demonstrated in a number of murine models of neurodegenerative disease. The focus of this review will be our recent observation of a possible tropism of such cells for neurodegenerative environments.
多能神经祖细胞或干细胞(或模拟其行为的细胞)能够沿着多种中枢神经系统(CNS)细胞类型谱系分化,包括神经元和神经胶质细胞。它们可以作为正常结构的组成部分植入宿主中枢神经系统的各处,而不会干扰其他神经生物学过程。通过利用它们的基本生物学特性,这些细胞或许能够以持续、直接的方式在整个中枢神经系统中传播治疗性基因产物。此外,它们可以以位点特异性和全局性的方式替代功能失调的神经元和神经胶质细胞。它们可能在发育过程中和成熟大脑中发生的神经退行性疾病中发挥治疗作用。神经干细胞不仅在其正常发育表达过程中对神经源性信号有反应,甚至在损伤后的后期被诱导或“重新激活”时也有反应,这可能使其在重建受损中枢神经系统区域方面具有实用性。因此,这些载体可能克服病毒和非神经细胞载体以及药理学和基因干预的许多局限性。这种广泛适用的基于神经干细胞的策略的可行性已在多种神经退行性疾病的小鼠模型中得到证实。本综述的重点将是我们最近对这类细胞在神经退行性环境中可能存在的嗜性的观察。