Long-term proliferation and dopaminergic differentiation of human mesencephalic neural precursor cells

Exp Neurol. 2001 Aug;170(2):317-25. doi: 10.1006/exnr.2001.7706.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomarkers / analysis
  • Cell Culture Techniques / methods
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Division / drug effects
  • Cell Division / physiology*
  • Cells, Cultured
  • Dopamine / analysis
  • Embryo, Mammalian
  • Epidermal Growth Factor / pharmacology
  • Fetus
  • Fibroblast Growth Factor 2 / pharmacology
  • Gestational Age
  • Glial Cell Line-Derived Neurotrophic Factor
  • Growth Inhibitors / pharmacology
  • Humans
  • Interleukin-1 / pharmacology
  • Interleukin-11 / pharmacology
  • Interleukin-6*
  • Kinetics
  • Leukemia Inhibitory Factor
  • Lymphokines / pharmacology
  • Mesencephalon / cytology
  • Mesencephalon / embryology*
  • Nerve Growth Factors*
  • Nerve Tissue Proteins / pharmacology
  • Neurons / cytology*
  • Oxygen / pharmacology
  • Prosencephalon / cytology
  • Prosencephalon / embryology*
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Time Factors
  • Tyrosine 3-Monooxygenase / analysis

Substances

  • Biomarkers
  • GDNF protein, human
  • Glial Cell Line-Derived Neurotrophic Factor
  • Growth Inhibitors
  • Interleukin-1
  • Interleukin-11
  • Interleukin-6
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • Lymphokines
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Fibroblast Growth Factor 2
  • Epidermal Growth Factor
  • Tyrosine 3-Monooxygenase
  • Oxygen
  • Dopamine