Induction of dopaminergic neurons from growth factor expanded neural stem/progenitor cell cultures derived from human first trimester forebrain.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/162416
- author
- Christophersen, Nicolaj LU ; Meijer, Xia ; Jørgensen, Jesper R ; Englund Johansson, Ulrica LU ; Grønborg, Mette ; Seiger, Ake ; Brundin, Patrik LU and Wahlberg, Lars U
- organization
- publishing date
- 2006
- 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
- 2022-01-27 01:22:56
@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}},
keywords = {{Neural stem cell; Neural progenitor; Neurospheres; Human; Tyrosine hydroxylase; Dopaminergic; Parkinson's disease; Differentiation method}},
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}},
}