PMID- 18652826
OWN - NLM
STAT- MEDLINE
DCOM- 20081008
LR  - 20131121
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 213
IP  - 2
DP  - 2008 Oct
TI  - Combined use of BDNF, ascorbic acid, low oxygen, and prolonged differentiation 
      time generates tyrosine hydroxylase-expressing neurons after long-term in vitro 
      expansion of human fetal midbrain precursor cells.
PG  - 354-62
LID - 10.1016/j.expneurol.2008.06.014 [doi]
AB  - 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 can 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.
FAU - Maciaczyk, Jaroslaw
AU  - Maciaczyk J
AD  - Laboratory of Molecular Neurosurgery, Department of Stereotactic and Functional 
      Neurosurgery, Neurocenter, University of Freiburg, Freiburg, Germany.
FAU - Singec, Ilyas
AU  - Singec I
FAU - Maciaczyk, Donata
AU  - Maciaczyk D
FAU - Nikkhah, Guido
AU  - Nikkhah G
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080703
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - PQ6CK8PD0R (Ascorbic Acid)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Ascorbic Acid/*administration & dosage
MH  - Brain-Derived Neurotrophic Factor/*administration & dosage
MH  - Cell Culture Techniques/methods
MH  - Cell Differentiation/drug effects/*physiology
MH  - Cells, Cultured
MH  - Fetus
MH  - Gene Expression Regulation, Enzymologic/drug effects/physiology
MH  - Humans
MH  - Mesencephalon/cytology/drug effects/metabolism
MH  - Neurons/cytology/drug effects/metabolism
MH  - Oxygen/*metabolism
MH  - Stem Cells/*cytology/drug effects/metabolism
MH  - Time
MH  - Time Factors
MH  - Tyrosine 3-Monooxygenase/*biosynthesis/genetics
EDAT- 2008/07/26 09:00
MHDA- 2008/10/09 09:00
CRDT- 2008/07/26 09:00
PHST- 2008/03/12 00:00 [received]
PHST- 2008/06/11 00:00 [revised]
PHST- 2008/06/17 00:00 [accepted]
PHST- 2008/07/26 09:00 [pubmed]
PHST- 2008/10/09 09:00 [medline]
PHST- 2008/07/26 09:00 [entrez]
AID - S0014-4886(08)00262-8 [pii]
AID - 10.1016/j.expneurol.2008.06.014 [doi]
PST - ppublish
SO  - Exp Neurol. 2008 Oct;213(2):354-62. doi: 10.1016/j.expneurol.2008.06.014. Epub 
      2008 Jul 3.