Precursor cell biology and the development of astrocyte transplantation therapies: lessons from spinal cord injury.
Precursor cell biology and the development of astrocyte transplantation therapies: lessons from spinal cord injury.
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DOI：
10.1007/s13311-011-0071-z
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发表时间：
2011-10
影响因子：
5.7
通讯作者：
Davies, Stephen J. A.
中科院分区：
文献类型：
--
作者：
Noble, Mark;Davies, Jeannette E.;Mayer-Proeschel, Margot;Proeschel, Christoph;Davies, Stephen J. A.
关键词：
This review summarizes current progress on development of astrocyte transplantation therapies for repair of the damaged central nervous system. Replacement of neurons in the injured or diseased central nervous system is currently one of the most popular therapeutic goals, but if neuronal replacement is attempted in the absence of appropriate supporting cells (astrocytes and oligodendrocytes), then the chances of restoring neurological functional are greatly reduced. Although the past 20 years have offered great progress on oligodendrocyte replacement therapies, astrocyte transplantation therapies have been both less explored and comparatively less successful. We have now developed successful astrocyte transplantation therapies by pre-differentiating glial restricted precursor (GRP) cells into a specific population of GRP cell-derived astrocytes (GDAs) by exposing the GRP cells to bone morphogenetic protein-4 (BMP) prior to transplantation. When transplanted into transected rat spinal cord, rat and human GDAsBMP promote extensive axonal regeneration, rescue neuronal cell survival, realign tissue structure, and restore behavior to pre-injury levels on a grid-walk analysis of volitional foot placement. Such benefits are not provided by GRP cells themselves, demonstrating that the lesion environment does not direct differentiation in a manner optimally beneficial for the restoration of function. Such benefits also are not provided by transplantation of a different population of astrocytes generated from GRP cells exposed to ciliary neurotrophic factor (GDAsCNTF), thus providing the first transplantation-based evidence of functional heterogeneity in astrocyte populations. Moreover, lessons learned from the study of rat cells are strongly predictive of outcomes using human cells. Thus, these studies provide successful strategies for the use of astrocyte transplantation therapies for restoration of function following spinal cord injury. The online version of this article (doi:10.1007/s13311-011-0071-z) contains supplementary material, which is available to authorized users.
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