Long-term proliferation and dopaminergic differentiation of human mesencephalic neural precursor cells.
We report on generation of dopamine neurons from long-term cultures of human fetal mesencephalic precursor cells. These CNS precursor cells were successfully expanded in vitro using the mitogens epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2). Incubation of these cultures in 3% atmospheric oxygen resulted in higher cellular yields than room air. Following incubation in differentiation media containing interleukin (IL)-1b (IL-1b), IL-11, leukemia inhibitory factor (LIF), and glial cell line-derived neurotrophic factor (GDNF), up to 1% of the precursor cells converted into cells immunoreactive for tyrosine hydroxylase (TH), a marker for dopamine neurons. The TH immunoreactive cells exhibited morphological and functional properties characteristic of dopamine neurons in culture. These precursor cells might serve as a useful source of human dopamine neurons for studying the development and degeneration of human dopamine neurons and may further serve as a continuous, on-demand source of cells for therapeutic transplantation in patients with Parkinson's disease.
Storch
A
A
Department of Neurology, University of Ulm Medical School, Ulm, Germany. alexander.storch@medizin.uni-ulm.de
Paul
G
G
Csete
M
M
Boehm
B O
BO
Carvey
P M
PM
Kupsch
A
A
Schwarz
J
J
D015415:Biomarkers / Q000032:analysis; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004298:Dopamine / Q000032:analysis; D004622:Embryo, Mammalian; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005865:Gestational Age; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D017370:Interleukin-11 / Q000494:pharmacology; D015850:Interleukin-6; D007700:Kinetics; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology*; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009474:Neurons / Q000166:cytology*; D010100:Oxygen / Q000494:pharmacology; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D015415:Biomarkers; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006131:Growth Inhibitors; D007375:Interleukin-1; D017370:Interleukin-11; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D014446:Tyrosine 3-Monooxygenase; D010100:Oxygen; D004298:Dopamine