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Induction of dopaminergic neurons from growth factor expanded neural stem/progenitor cell cultures derived from human first trimester forebrain.

Christophersen, Nicolaj LU ; Meijer, Xia ; Jørgensen, Jesper R ; Englund Johansson, Ulrica LU ; Grønborg, Mette ; Seiger, Ake ; Brundin, Patrik LU and Wahlberg, Lars U (2006) In Brain Research Bulletin 70(4-6). p.457-466
Abstract
Multipotent stem/progenitor cells derived from human first trimester forebrain can be expanded as free-floating aggregates, so called neurospheres. These cells can differentiate into neurons, astrocytes and oligodendrocytes. In vitro differentiation protocols normally yield γ-aminobutyric acid-immunoreactive neurons, whereas only few tyrosine hydroxylase (TH) expressing neurons are found. The present report describes conditions under which 4–10% of the cells in the culture become TH immunoreactive (ir) neurons within 24 h. Factors including acidic fibroblast growth factor (aFGF) in combination with agents that increase intracellular cyclic AMP and activate protein kinase C, in addition to a substrate that promotes neuronal differentiation... (More)
Multipotent stem/progenitor cells derived from human first trimester forebrain can be expanded as free-floating aggregates, so called neurospheres. These cells can differentiate into neurons, astrocytes and oligodendrocytes. In vitro differentiation protocols normally yield γ-aminobutyric acid-immunoreactive neurons, whereas only few tyrosine hydroxylase (TH) expressing neurons are found. The present report describes conditions under which 4–10% of the cells in the culture become TH immunoreactive (ir) neurons within 24 h. Factors including acidic fibroblast growth factor (aFGF) in combination with agents that increase intracellular cyclic AMP and activate protein kinase C, in addition to a substrate that promotes neuronal differentiation appear critical for efficient TH induction. The cells remain THir after trypsinization and replating, even when their subsequent culturing takes place in the absence of inducing factors. Consistent with a dopaminergic phenotype, mRNAs encoding aromatic acid decarboxylase, but not dopamine-β-hydroxylase were detected by quantitative real time RT-PCR. Ten weeks after the cells had been grafted into the striatum of adult rats with unilateral nigrostriatal lesions, only very few of the surviving human neurons expressed TH. Our data suggest that a significant proportion of expandable human neural progenitors can differentiate into TH-expressing cells in vitro and that they could be useful for drug and gene discovery. Additional experiments, however, are required to improve the survival and phenotypic stability of these cells before they can be considered useful for cell replacement therapy in Parkinson's disease. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Neural stem cell, Neural progenitor, Neurospheres, Human, Tyrosine hydroxylase, Dopaminergic, Parkinson's disease, Differentiation method
in
Brain Research Bulletin
volume
70
issue
4-6
pages
457 - 466
publisher
Elsevier
external identifiers
  • wos:000241546500022
  • scopus:33749242798
ISSN
0361-9230
DOI
10.1016/j.brainresbull.2006.07.001
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neurobiology (013212024), Neuronal Survival (013212041), Ophthalmology (Lund) (013043000)
id
2abcedbf-3fae-435f-aa16-a071bfd62d6e (old id 162416)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17027782&dopt=Abstract
date added to LUP
2016-04-01 12:16:24
date last changed
2019-11-26 03:27:28
@article{2abcedbf-3fae-435f-aa16-a071bfd62d6e,
  abstract     = {Multipotent stem/progenitor cells derived from human first trimester forebrain can be expanded as free-floating aggregates, so called neurospheres. These cells can differentiate into neurons, astrocytes and oligodendrocytes. In vitro differentiation protocols normally yield γ-aminobutyric acid-immunoreactive neurons, whereas only few tyrosine hydroxylase (TH) expressing neurons are found. The present report describes conditions under which 4–10% of the cells in the culture become TH immunoreactive (ir) neurons within 24 h. Factors including acidic fibroblast growth factor (aFGF) in combination with agents that increase intracellular cyclic AMP and activate protein kinase C, in addition to a substrate that promotes neuronal differentiation appear critical for efficient TH induction. The cells remain THir after trypsinization and replating, even when their subsequent culturing takes place in the absence of inducing factors. Consistent with a dopaminergic phenotype, mRNAs encoding aromatic acid decarboxylase, but not dopamine-β-hydroxylase were detected by quantitative real time RT-PCR. Ten weeks after the cells had been grafted into the striatum of adult rats with unilateral nigrostriatal lesions, only very few of the surviving human neurons expressed TH. Our data suggest that a significant proportion of expandable human neural progenitors can differentiate into TH-expressing cells in vitro and that they could be useful for drug and gene discovery. Additional experiments, however, are required to improve the survival and phenotypic stability of these cells before they can be considered useful for cell replacement therapy in Parkinson's disease.},
  author       = {Christophersen, Nicolaj and Meijer, Xia and Jørgensen, Jesper R and Englund Johansson, Ulrica and Grønborg, Mette and Seiger, Ake and Brundin, Patrik and Wahlberg, Lars U},
  issn         = {0361-9230},
  language     = {eng},
  number       = {4-6},
  pages        = {457--466},
  publisher    = {Elsevier},
  series       = {Brain Research Bulletin},
  title        = {Induction of dopaminergic neurons from growth factor expanded neural stem/progenitor cell cultures derived from human first trimester forebrain.},
  url          = {http://dx.doi.org/10.1016/j.brainresbull.2006.07.001},
  doi          = {10.1016/j.brainresbull.2006.07.001},
  volume       = {70},
  year         = {2006},
}