Transplantation options for therapeutic central nervous system remyelination

Transplantation options for therapeutic central nervous system remyelination
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DOI:
10.1177/096368970000900214
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发表时间:
2000-03-01
影响因子:
3.3
通讯作者:
Franklin, RJM
Franklin, RJM
中科院分区:
医学4区
文献类型:
--
作者:
Blakemore, WF;Franklin, RJM

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持续性脱髓鞘除了是多发性硬化症和白质营养不良的主要病理外,也是脊髓损伤的一个特征,有证据表明它导致了功能缺陷。在实验动物中,通过移植含有中央或外周髓鞘细胞的培养物,可以使脱髓鞘的中枢神经系统轴突重新脱髓鞘。通过功能测试,我们已经能够证明,移植介导的髓鞘再分化可以恢复因脱髓鞘而丧失的功能。因此,神经胶质细胞移植可能为慢性脱髓鞘区域提供一种治疗策略。本文综述了在人类进行神经胶质移植之前必须解决的问题。这些问题包括:使用什么细胞,这些细胞从哪里来,以及我们能预测将实现多少重新髓鞘形成?结论:最有希望的方法是使用从胚胎中枢神经系统分离的神经多潜能干细胞,在体外扩增为神经球,然后在植入前致力于少突胶质细胞的谱系分化。然而,即使使用这种具有相当大的髓鞘形成潜力的制剂,目前也无法确切地预测将实现的再髓鞘形成的程度。
persistent demyelination, in addition to being the major pathology of multiple sclerosis and the leucodystrophies, is also a feature of spinal cord trauma where there is evidence that it contributes to the functional deficit, In experimental animals it is possible to remyelinate demyelinated CNS axons by transplanting cultures containing central or peripheral myelinogenic cells. Using functional testing we have been able to show that transplant-mediated remyelination results in restoration of function lost as a consequence of demyelination. Glial cell transplantation may therefore provide a therapeutic strategy for remyelinating areas of chronic demyelination. This article reviews issues that have to be addressed before glial transplantation can he undertaken in humans. These include: what cells to use, where would the cells come from, and can we predict how much remyelination will be achieved? It concludes that the most promising approach will be to use neural multipotential stem cells isolated from embryonic CNS, expanded in vitro as neurospheres and then committed to oligodendrocyte lineage differentiation prior to implantation. However, even with such preparations, which have considerable myelinating potential, the extent of remyelination that will be achieved cannot currently be predicted with any degree of certainty.