Oligodendrocytes and stem cell transplantation: their potential in the treatment of leukoencephalopathies
Oligodendrocytes and stem cell transplantation: their potential in the treatment of leukoencephalopathies
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DOI：
10.1007/s10545-005-7058-z
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发表时间：
2005-01-01
影响因子：
4.2
通讯作者：
Duncan, ID
中科院分区：
文献类型：
--
作者：
Duncan, ID
细胞移植作为治疗许多人类退行性疾病的手段正在被广泛探索。脑白质营养不良是神经系统疾病的实例，其中需要新的治疗策略（细胞或分子）来修复受影响患者的中枢神经系统（CNS）。人们寄希望于利用人类胚胎干细胞作为神经元和神经胶质细胞的外源性来源，以取代中枢神经系统中功能失调或死亡的细胞。在脑白质病的情况下，目标是从ES细胞产生少突胶质细胞或其他髓鞘形成细胞，如施万细胞，以在移植时使CNS轴突髓鞘化或再髓鞘化。实验数据表明，小鼠ES细胞具有这种能力，但目前不可能从人ES细胞分化出足够数量的少突胶质细胞。事实上，从来自胎儿大脑的人类神经干细胞中分离少突胶质细胞可能更可行，但这些细胞的来源短缺，并且像ES细胞一样，在伦理上存在争议。尽管如此，这两种来源中的任何一种似乎都将最终产生足够数量的神经干细胞或少突胶质细胞祖细胞，这些细胞比成人大脑中的细胞具有更大的修复能力。一旦有关人类ES细胞分化的主要技术问题被克服，最有可能的第一个临床目标将是Pelizaeus-Merzbacher病。然而，功能改善可能需要细胞在整个CNS中的广泛散布;因此，肾上腺脑白质营养不良等疾病也可被视为治疗靶点。
Cell transplantation is being extensively explored as a means of treating many human degenerative diseases. The leukodystrophies are examples of neurological disorders where new therapeutic strategies, either cellular or molecular, will be required to repair the central nervous system (CNS) of affected patients. Much hope is being pinned on the use of human embryonic stem (ES) cells as the exogenous source of neurons and glia to replace dysfunctional or dying cells in the CNS. In the case of leukoencephalopathies, the goal is to generate oligodendrocytes or other myelinating cells such as Schwann cells from ES cells, to myelinate or remyelinate CNS axons on transplantation. Experimental data suggests that mouse ES cells have this capacity, but at present differentiation of oligodendrocytes in sufficient numbers from human ES cells is not possible. It may in fact be more feasible to isolate oligodendrocytes from human neural stem cells derived from the fetal brain, but the source of these is in short supply and, like that of ES cells, is ethically controversial. None the less, it appears certain that either of these two sources will eventually give rise to sufficient numbers of neural stem cells or oligodendrocyte progenitors that have greater capacity for repair than such cells derived from the adult brain. Once the primary technical issues concerning human ES cell differentiation have been overcome, the most likely first clinical target will be Pelizaeus-Merzbacher disease. However, widespread dissemination of cells throughout the CNS may be required for functional improvement; hence diseases such as adrenoleukodystrophy may also be considered as therapeutic targets.