title: Dopamine release from transplanted neural stem cells in Parkinsonian rat striatum in vivo.
abstract: Embryonic stem cell-based therapies exhibit great potential for the treatment of Parkinson's disease (PD) because they can significantly rescue PD-like behaviors. However, whether the transplanted cells themselves release dopamine in vivo remains elusive. We and others have recently induced human embryonic stem cells into primitive neural stem cells (pNSCs) that are self-renewable for massive/transplantable production and can efficiently differentiate into dopamine-like neurons (pNSC-DAn) in culture. Here, we showed that after the striatal transplantation of pNSC-DAn, (i) pNSC-DAn retained tyrosine hydroxylase expression and reduced PD-like asymmetric rotation; (ii) depolarization-evoked dopamine release and reuptake were significantly rescued in the striatum both in vitro (brain slices) and in vivo, as determined jointly by microdialysis-based HPLC and electrochemical carbon fiber electrodes; and (iii) the rescued dopamine was released directly from the grafted pNSC-DAn (and not from injured original cells). Thus, pNSC-DAn grafts release and reuptake dopamine in the striatum in vivo and alleviate PD symptoms in rats, providing proof-of-concept for human clinical translation.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Xinjiang
authors.initials: X
authors.lastname: Kang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Huadong
authors.initials: H
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Sasa
authors.initials: S
authors.lastname: Teng
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Zijun
authors.initials: Z
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Panli
authors.initials: P
authors.lastname: Zuo
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Qihui
authors.initials: Q
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Meiqin
authors.initials: M
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Haiqiang
authors.initials: H
authors.lastname: Dou
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Feipeng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Shu
authors.initials: S
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Jingli
authors.initials: J
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Qian
authors.initials: Q
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Jing
authors.initials: J
authors.lastname: Lü
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Yu
authors.initials: Y
authors.lastname: Mu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Mu
authors.initials: M
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Shirong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Molecular Medicine Research Center, West China Hospital, Chengdu, Sichuan 610041, China;
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Capital Sport University, Capital University of Physical Education and Sports, Beijing 100088, China;
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Changhe
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Second Military Medical University, Shanghai 200092, China; zzhou@pku.edu.cn k5zhang@ad.ustc.edu liwenlin@smmu.edu.cn.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Li
authors.affiliation: Molecular Medicine Research Center, West China Hospital, Chengdu, Sichuan 610041, China; Institute of Genomic Medicine and Shiley Eye Center, University of California, San Diego, La Jolla, CA 92093; and Veterans Administration Healthcare System, San Diego, CA 92161 zzhou@pku.edu.cn k5zhang@ad.ustc.edu liwenlin@smmu.edu.cn.
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China; zzhou@pku.edu.cn k5zhang@ad.ustc.edu liwenlin@smmu.edu.cn.
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D064593:Heterografts; D006801:Humans; D008297:Male; D058953:Neural Stem Cells / Q000378:metabolism* / Q000637:transplantation; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: CFE; Parkinson's disease; dopamine; neural stem cells; striatum in vivo