期刊
EXPERIMENTAL NEUROLOGY
卷 213, 期 2, 页码 354-362出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2008.06.014
关键词
human fetal mesencephalon; neural precursor cell; dopamine neuron; cell therapy; Parkinson's disease; BDNF
资金
- Deutsche Forschungsgemeinschaft [Ni 330, SFB 505]
- Graduate School Freiburg [DFG 843]
- German Parkinson's Foundation
- American Parkinson's Disease Association
Freshly isolated fetal midbrain neural precursor cells (NPCs) that maintain the potential to differentiate into dopamine (DA) neurons represent a valuable source for cell therapy in Parkinson's disease. However, it is poorly understood why midbrain NPCs lose their dopaminergic differentiation potential after long-term Culture. Here we report that human fetal midbrain NPCs call be extensively proliferated with fibroblast growth factor 2 (FGF-2), epidermal growth factor (EGF), and leukemia inhibitory factor (LIF) and efficiently differentiated into tyrosine hydroxylase-immunoreactive (TH-ir) neurons. We tested differentiation conditions including the use of low oxygen, ascorbic acid, and prolonged in vitro differentiation time which resulted in a 10-fold increase in the number of MAP2-positive neurons (up to 40-50% of total cells as compared to controls). Under these conditions TH-ir cells Constituted 4.3 +/- 0.5% of the neuronal Population and displayed immature morphologies. Notably, the use of brain-derived neurotrophic factor (BDNF) further increased the proportion of TH-ir neurons (up to 15% of total neurons). In contrast to previous reports, our findings demonstrate that long-term expanded fetal NPCs can generate TH-expressing cells under the appropriate Culture conditions and without genetic Manipulations. (c) 2008 Elsevier Inc. All rights reserved.
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