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TISSUE-SPECIFIC STEM CELLS

Specification of a Dopaminergic Phenotype from Adult Human Mesenchymal Stem Cells

^aGraduate School of Biomedical Sciences,
^bDepartment of Pharmacology and Physiology,
^cDepartment of Medicine Hematology/Oncology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey, USA

Key Words. Dopamine • Stem cells • Parkinson disease • Neural repair

Correspondence: Pranela Rameshwar, Ph.D., University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, MSB E-585, Newark, New Jersey 07103, USA. Telephone: (973) 972-0625; Fax: (973) 972-8854; e-mail: rameshwa{at}umdnj.edu

Received March 24, 2007; accepted for publication July 16, 2007.
First published online in STEM CELLS EXPRESS   July 26, 2007.



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.

Disclosure of potential conflicts of interest is found at the end of this article.