title: Human cord blood-derived multipotent stem cells (CB-SCs) treated with all-trans-retinoic acid (ATRA) give rise to dopamine neurons.
abstract: 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 μM 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.
authors.affiliation: Department of Neurology, Jinan Central Hospital, Shandong University, 105 Jiefang Road, Jinan 250013, PR China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.forename: Jianfen
authors.initials: J
authors.lastname: Bi
authors.forename: Yana
authors.initials: Y
authors.lastname: Chen
authors.forename: Sumit
authors.initials: S
authors.lastname: Jain
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000637:transplantation; D005312:Fetal Blood / Q000166:cytology*; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000096:biosynthesis; D010300:Parkinson Disease / Q000628:therapy; D014212:Tretinoin / Q000494:pharmacology*; D051155:Wnt1 Protein / Q000096:biosynthesis
chemical_list: C513076:EN1 protein, human; D018398:Homeodomain Proteins; C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; C495247:WNT1 protein, human; D051155:Wnt1 Protein; D014212:Tretinoin