Parkinson's disease (PD) results from the chronic degeneration of dopaminergic neurons. A replacement for these neurons has the potential to provide a clinical cure and/or lasting treatment for symptoms of the disease. Human cord blood-derived multipotent stem cells (CB-SCs) display embryonic stem cell characteristics, including multi-potential differentiation. To explore their therapeutic potential in PD, we examined whether CB-SCs could be induced to differentiate into dopamine neurons in the presence of all-trans retinoic acid (ATRA). Prior to treatment, CB-SCs expressed mRNA and protein for the key dopaminergic transcription factors Nurr1, Wnt1, and En1. Following treatment with 10 mu M ATRA for 12 days, CB-SCs displayed elongated neuronal-like morphologies. Immunocytochemistry revealed that 48 +/- 11% of ATRA-treated cells were positive for tyrosine hydroxylase (TH), and 36 +/- 9% of cells were positive for dopamine transporter (DAT). In contrast, control CB-SCs (culture medium only) expressed only background levels of TH and DAT. Finally, ATRA-treated CB-SCs challenged with potassium released increased levels of dopamine compared to control. These data demonstrate that ATRA induces differentiation of CB-SCs into dopaminergic neurons. This finding may lead to the development of an alternative approach to stem cell therapy for Parkinson's disease. (C) 2012 Elsevier Inc. All rights reserved.