PMID- 23633297 OWN - NLM STAT- MEDLINE DCOM- 20140103 LR - 20181202 IS - 1097-4547 (Electronic) IS - 0360-4012 (Linking) VI - 91 IP - 7 DP - 2013 Jul TI - Conditioned medium from human amniotic epithelial cells may induce the differentiation of human umbilical cord blood mesenchymal stem cells into dopaminergic neuron-like cells. PG - 978-86 LID - 10.1002/jnr.23225 [doi] AB - Dopaminergic (DA) neuron therapy has been established as a new clinical tool for treating Parkinson's disease (PD). Prior to cell transplantation, there are two primary issues that must be resolved: one is the appropriate seed cell origin, and the other is the efficient inducing technique. In the present study, human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) were used as the available seed cells, and conditioned medium from human amniotic epithelial cells (ACM) was used as the inducing reagent. Results showed that the proportion of DA neuron-like cells from hUCB-MSCs was significantly increased after cultured in ACM, suggested by the upregulation of DAT, TH, Nurr1, and Pitx3. To identify the process by which ACM induces DA neuron differentiation, we pretreated hUCB-MSCs with k252a, the Trk receptor inhibitor of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), and found that the proportion of DA neuron-like cells was significantly decreased compared with ACM-treated hUCB-MSCs, suggesting that NGF and BDNF in ACM were involved in the differentiation process. However, we could not rule out the involvement of other unidentified factors in the ACM, because ACM + k252a treatment does not fully block DA neuron-like cell differentiation compared with control. The transplantation of ACM-induced hUCB-MSCs could ameliorate behavioral deficits in PD rats, which may be associated with the survival of engrafted DA neuron-like cells. In conclusion, we propose that hUCB-MSCs are a good source of DA neuron-like cells and that ACM is a potential inducer to obtain DA neuron-like cells from hUCB-MSCs in vitro for an ethical and legal cell therapy for PD. CI - Copyright (c) 2013 Wiley Periodicals, Inc. FAU - Yang, Shu AU - Yang S AD - Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. FAU - Sun, Hai-Mei AU - Sun HM FAU - Yan, Ji-Hong AU - Yan JH FAU - Xue, Hong AU - Xue H FAU - Wu, Bo AU - Wu B FAU - Dong, Fang AU - Dong F FAU - Li, Wen-Shuai AU - Li WS FAU - Ji, Feng-Qing AU - Ji FQ FAU - Zhou, De-Shan AU - Zhou DS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130430 PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Culture Media, Conditioned) RN - 0 (Dopamine Plasma Membrane Transport Proteins) RN - 0 (Homeodomain Proteins) RN - 0 (NR4A2 protein, human) RN - 0 (Nuclear Receptor Subfamily 4, Group A, Member 2) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factors) RN - 0 (homeobox protein PITX3) RN - 8HW4YBZ748 (Oxidopamine) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - EC 2.7.10.1 (Receptor, trkA) RN - EC 2.7.10.1 (Receptor, trkB) RN - N21FAR7B4S (Apomorphine) SB - IM MH - Amnion/*cytology MH - Analysis of Variance MH - Animals MH - Apomorphine MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Cell Differentiation/*drug effects MH - Culture Media, Conditioned/*pharmacology MH - Disease Models, Animal MH - Dopamine Plasma Membrane Transport Proteins/genetics/metabolism MH - Dopaminergic Neurons/*drug effects MH - Enzyme-Linked Immunosorbent Assay MH - Epithelial Cells/*chemistry MH - Fetal Blood/*cytology MH - Fetus MH - Flow Cytometry MH - Homeodomain Proteins/genetics/metabolism MH - Humans MH - Mesenchymal Stem Cell Transplantation/methods MH - Mesenchymal Stem Cells/*drug effects MH - Nuclear Receptor Subfamily 4, Group A, Member 2/genetics/metabolism MH - Oxidopamine/toxicity MH - Parkinson Disease/etiology/physiopathology/surgery MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkA/genetics/metabolism MH - Receptor, trkB/metabolism MH - Stereotyped Behavior/drug effects/physiology MH - Transcription Factors/genetics/metabolism MH - Tyrosine 3-Monooxygenase/genetics/metabolism EDAT- 2013/05/02 06:00 MHDA- 2014/01/05 06:00 CRDT- 2013/05/02 06:00 PHST- 2013/01/10 00:00 [received] PHST- 2013/02/05 00:00 [revised] PHST- 2013/02/25 00:00 [accepted] PHST- 2013/05/02 06:00 [entrez] PHST- 2013/05/02 06:00 [pubmed] PHST- 2014/01/05 06:00 [medline] AID - 10.1002/jnr.23225 [doi] PST - ppublish SO - J Neurosci Res. 2013 Jul;91(7):978-86. doi: 10.1002/jnr.23225. Epub 2013 Apr 30.