Analysis of the neurogenic potential of multipotent skin-derived precursors

被引:101
作者
Fernandes, Karl J. L.
Kobayashi, Nao R.
Gallagher, Conor J.
Barnabe-Heider, Fanie
Aumont, Anne
Kaplan, David R.
Miller, Freda D.
机构
[1] Univ Toronto, Program Dev Biol, Toronto, ON M5G 1X8, Canada
[2] Univ Toronto, Program Canc Res, Toronto, ON M5G 1X8, Canada
[3] Univ Toronto, Hosp Sick Children, Program Brain & Behav, Toronto, ON M5G 1X8, Canada
[4] Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5G 1X8, Canada
[5] Univ Toronto, Dept Physiol, Toronto, ON M5G 1X8, Canada
[6] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada
[7] Cell Restorat Lab, Halifax, NS B3H 1X5, Canada
基金
加拿大健康研究院;
关键词
stem cells; neurogenesis; neural crest; transplantation; hippocampal slice; growth factors;
D O I
10.1016/j.expneurol.2006.03.018
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Multipotent precursors similar to stem cells of the embryonic neural crest (NC) have been identified in several postnatal tissues, and are potentially useful for research and therapeutic purposes. However, their neurogenic potential, including their ability to produce electrophysiologically active neurons, is largely unexplored. We investigated this issue with regard to skin-derived precursors (SKPs), multipotent NC-related precursors isolated from the dermis of skin. SKP cultures follow an appropriate pattern and time-course of neuronal differentiation, with proliferating nestin-expressing SKPs generating post-mitotic neuronal cells that co-express pan-neuronal and peripheral autonomic lineage markers. These SKP-derived neuron-like cells survive and maintain their peripheral phenotype for at least 5 weeks when transplanted into the CNS environment of normal or kainate-in jured hippocampal slices. Undifferentiated SKPs retain key neural precursor proper-ties after multi-passage expansion, including growth factor dependence, nestin expression, neurogenic potential, and responsiveness to embryonic neural crest fate determinants. Despite undergoing an apparently appropriate neurogenic process, however, SKP-detived neuron-like cells possess an immature electrophysiological profile. These findings indicate that SKPs retain latent neurogenic properties after residing in a non-neural tissue, but that additional measures will be necessary to promote their differentiation into electrophysiologically active neurons. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:32 / 48
页数:17
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