Liver X receptors agonist promotes differentiation of rat bone marrow derived mesenchymal stem cells into dopaminergic neuron-like cells
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Oumei Cheng1,2,*, Xiaoyan Tian1,*, Ying Luo1, Shaoshan Mai1, Yang Yang1, Shengnan Kuang1, Qi Chen1, Jie Ma1, Beibei Chen2, Rong Li2, Lu Yang1, Huan Li1, Congli Hu1, Jiahua Zhang1, Zhihao Chen1, Yuke Li1, Hui Xia1, Ying Xu3 and Junqing Yang1
1Department of Pharmacology, Chongqing Medical University, The Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China
2Department of Neurology, The First Affiliated China Hospital, Chongqing Medical University, Chongqing, 400016, China
3Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA
*These authors share co-first authorship
Junqing Yang, email: [email protected]
Keywords: Parkinson’s disease; dopaminergic neurons; liver X receptors; bone marrow derived mesenchymal stem cells and cell differentiation
Received: August 23, 2017 Accepted: November 14, 2017 Published: December 09, 2017
Dopaminergic (DA) neurons derived from bone marrow derived mesenchymal stem cells (BMSCs) maybe a valuable source for cell replacement therapy in Parkinson disease. Recent studies showed that new functions of LXR and their ligands have been proposed to prevent PD in the adult nervous system. The present study was designed to observe the effect of liver X receptors (LXR) agonist on differentiation of rat BMSCs into DA neurons. Expressions of the neuronal markers (Tuj1 and Nestin), the specific marker of DA neurons (tyrosine hydroxylase, TH), LXR α and LXR β were measured by immunocytochemical assay and TH/Tuj1 positive cells were determined by quantitative cell count analyses. mRNA expressions of LXR α, LXR β, TH, DAT, Nurr1, Pitx3, En1 and Lmx1b were measured by qPCR. Compared with growth factors (GF) treated group, combined use of LXR and GF induced rat BMSCs to TH-expressing cells with 87.42% of efficiency in 6 days of period of induction. LXR agonist alone did not induce the differentiation. Compared with GF alone, combined use of LXR and GF increased expressions of LXR α and LXR β protein and mRNA and TH, DAT, Nurr1, and Pitx3 mRNA, decreased expressions of En1 and Lmx1b mRNA. Our experimental results indicated that LXR activation leads to improve induction efficiency and shorten induction period of rat BMSCs into DA neuron-like cells through regulating DA development-related genes expressions and that LXR can be considered as a candidate target for drug development to improve differentiation of BMSCs into DA neurons.
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