The controlled conversion of human neural progenitor cells derived from foetal ventral mesencephalon into dopaminergic neurons in vitro.
The expansion and differentiation of neural progenitor cells in vitro provides an approach to study the development and differentiation of neurons. The ventral mesencephalic area of the brain is an important source of neural progenitor cells and the differentiated neural progenitor cell has paramount potential for use in transplant therapies such as those used in the treatment of neurodegenerative diseases. Here, the controlled conversion of human foetal progenitor cells derived from ventral mesencephalon into dopaminergic neurons is reported. The immunoreactivity to tyrosine hydroxylase (TH) and levels of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), secreted into culture medium, were used to assess dopaminergic neuronal phenotype. Expansion of the neural progenitor cells for 3 weeks in the presence of basic fibroblast growth factor (2 ng/ml) followed by its withdrawal resulted in approximately 60% of cells staining positive for TH, when challenged in concert with brain-derived neurotrophic factor (50 ng/ml), DA (10 microM) and forskolin (10 microM) for a further 3 weeks. A corresponding 41-fold increase in DA and DOPAC was measured in the incubation medium by HPLC. Therefore, the successful conversion of human foetal progenitor cells in vitro resulting in the desired dopaminergic neuronal phenotype, could provide a solution to the problem of limited availability of human foetuses for clinical surgical transplantation therapies, which are currently in progress for the treatment of neurodegenerative diseases such as Parkinson's disease.
Riaz
Samina S
SS
Department of Biochemistry, Imperial College of Science, Technology and Medicine, Exhibition Road, South Kensington, London, SW7 2AY, UK. s.s.riaz@ic.ac.uk
Jauniaux
Eric
E
Stern
Gerald M
GM
Bradford
Henry F
HF
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D016380:Brain Tissue Transplantation; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D004298:Dopamine / Q000032:analysis*; D016332:Fetal Tissue Transplantation; D005333:Fetus / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D008636:Mesencephalon / Q000166:cytology*; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D010300:Parkinson Disease / Q000628:therapy; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D019208:Brain-Derived Neurotrophic Factor; D015102:3,4-Dihydroxyphenylacetic Acid; D005576:Colforsin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine