Central nervous system cell transplantation: a novel therapy for storage diseases?
Central nervous system cell transplantation: a novel therapy for storage diseases?
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中枢神经系统细胞移植：贮积病的新疗法？
DOI：
10.1097/00019052-199604000-00013
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发表时间：
1996
影响因子：
4.8
通讯作者：
Wolfe,JH
中科院分区：
文献类型：
--
作者：
Snyder,EY;Wolfe,JH
许多将基因转移到大脑的方法正在研究中。一种采用基于神经干细胞的策略。移植内在分泌缺失或治疗性基因产物的神经祖细胞，或经离体遗传工程改造以分泌缺失或治疗性基因产物的神经祖细胞，可提供长期治疗许多神经遗传性疾病的中枢神经系统表现的策略。多能神经祖细胞或干细胞（或模仿其行为的细胞）能够沿沿着多种中枢神经系统细胞类型谱系分化。它们可以作为整个宿主中枢神经系统正常结构的组成部分植入，而不会干扰其他神经生物学过程。它们也可以很容易地离体遗传操纵。通过利用它们的基本生物学特性，这些细胞可能能够在整个中枢神经系统中以持续、直接和可能受调节的方式递送治疗性基因产物。此外，尽管它们可以将这些基因产物散布到整个大脑，但它们仍然将这种分布限制在中枢神经系统。因此，这些媒介物可以克服病毒和非神经细胞载体以及药理学和遗传干预的许多限制。这种基于神经干细胞的策略的可行性已经通过纠正原型遗传性神经退行性疾病粘多糖样变性VII型的小鼠模型的广泛中枢神经系统病理学而得到证实。这些研究有助于建立使用这些细胞作为在许多年龄的中枢神经系统中转移其他治疗或发育相关分子的范例。
Many methods of gene transfer to the brain are under study. One employs a neural stem cell based strategy. Transplanting neural progenitor cells that intrinsically secrete missing or therapeutic gene products, or are genetically engineered ex vivo to do so, may provide a strategy for long-term treatment of central nervous system manifestations of a number of neurogenetic diseases. Multipotent neural progenitors or stem cells (or cells that mimic their behavior) are capable of differentiating along multiple central nervous system cell-type lineages. They can engraft as integral members of normal structures throughout the host central nervous system without disturbing other neurobiological processes. They can also be easily genetically manipulated ex vivo. By exploiting their basic biological properties, these cells may be able to deliver therapeutic gene products in a sustained, direct, and perhaps regulated fashion throughout the central nervous system. Furthermore, although they may disseminate these gene products throughout the brain, they nevertheless restrict that distribution to only the central nervous system. 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 neural stem cell-based strategy has been demonstrated by correcting the widespread central nervous system pathology of a murine model of a prototypical inherited neurodegenerative disease, mucopolysaccharidosis type VII. These studies have helped to establish the use of such cells as a paradigm for transferring other molecules of therapeutic or developmental interest throughout the central nervous system at many ages.