Human cord blood-derived multipotent stem cells (CB-SCs) treated with all-trans-retinoic acid (ATRA) give rise to dopamine neurons

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• 作者：Xiaohong Li^a ; ¹ ; Heng Li^a ; ¹ ; Jianfen Bi^b ; Yana Chen^c ; Sumit Jain^d ; Yong Zhao^d ; ^{yongzhao@uic.edu}
• 关键词：ATRA ; all-trans retinoic acid ; CB-SCs ; cord blood-derived multipotent stem cells ; DA ; dopamine ; DAT ; dopamine transporter ; ES ; embryonic stem cell ; GFAP ; glial fibrillary acidic protein ; iPSCs ; induced pluripotent stem cells ; MAP2 ; microtubule-associated
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：2 March, 2012
• 卷：419
• 期：1
• 页码：110-116
• 文件大小：937 K

摘要

Parkinson鈥檚 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 渭M ATRA for 12 days, CB-SCs displayed elongated neuronal-like morphologies. Immunocytochemistry revealed that 48 卤 11%of ATRA-treated cells were positive for tyrosine hydroxylase (TH), and 36 卤 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鈥檚 disease.