Specification of a dopaminergic phenotype from adult human mesenchymal stem cells

Research output: Contribution to journalArticlepeer-review

142 Scopus citations

Abstract

Dopamine (DA) neurons derived from stem cells are a valuable source for cell replacement therapy in Parkinson disease, to study the molecular mechanisms of DA neuron development, and for screening pharmaceutical compounds that target DA disorders. Compared with other stem cells, MSCs derived from the adult human bone marrow (BM) have significant advantages and greater potential for immediate clinical application. We report the identification of in vitro conditions for inducing adult human MSCs into DA cells. Using a cocktail that includes sonic hedgehog and fibroblast growth factors, human BM-derived MSCs were induced in vitro to become DA cells in 12 days. Based on tyrosine hydroxylase (TH) expression, the efficiency of induction was determined to be ∼67%. The cells develop a neuronal morphology expressing the neuronal markers NeuN and β III tubulin, but not glial markers, glial fibrillary acidic protein and Olig2. As the cells acquire a postmitotic neuronal fate, they downregulate cell cycle activator proteins cyclin B, cyclin-dependent kinase 2, and proliferating cell nuclear antigen. Molecular characterization revealed the expression of DA-specific genes such as TH, Pitx3, Nurr1, DA transporter, and vesicular monoamine transporter 2. The induced MSCs also synthesize and secrete DA in a depolarization-independent manner. The latter observation is consistent with the low expression of voltage gated Na+ and Ca2+ channels in the induced MSCs and suggests that the cells are at an immature stage of development likely representing DA neuronal progenitors. Taken together, the results demonstrate the ability of adult human BM-derived MSCs to form DA cells in vitro.

Original languageEnglish (US)
Pages (from-to)2797-2808
Number of pages12
JournalSTEM CELLS
Volume25
Issue number11
DOIs
StatePublished - Nov 2007

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Cell Biology
  • Developmental Biology

Keywords

  • Dopamine
  • Neural repair
  • Parkinson disease
  • Stem cells

Fingerprint

Dive into the research topics of 'Specification of a dopaminergic phenotype from adult human mesenchymal stem cells'. Together they form a unique fingerprint.

Cite this