title: Lmx1a enhances the effect of iNSCs in a PD model.
abstract: Lmx1a plays a central role in the specification of dopaminergic (DA) neurons, which potentially could be employed as a key factor for trans-differentiation to DA neurons. In our previous study, we have converted somatic cells directly into neural stem cell-like cells, namely induced neural stem cells (iNSCs), which further can be differentiated into subtypes of neurons and glia in vitro. In the present study, we continued to test whether these iNSCs have therapeutic effects when transplanted into a mouse model of Parkinson's disease (PD), especially when Lmx1a was introduced into these iNSCs under a Nestin enhancer. iNSCs that over-expressed Lmx1a (iNSC-Lmx1a) gave rise to an increased yield of dopaminergic neurons and secreted a higher level of dopamine in vitro. When transplanted into mouse models of PD, both groups of mice showed decreased ipsilateral rotations; yet mice that received iNSC-Lmx1a vs. iNSC-GFP exhibited better recovery. Although few iNSCs survived 11weeks after transplantation, the improved motor performance in iNSC-Lmx1a group did correlate with a greater tyrosine hydroxylase (TH) signal abundance in the lesioned area of striatum, suggesting that iNSCs may have worked through a non-autonomous manner to enhance the functions of remaining endogenous dopaminergic neurons in brain.
authors.affiliation: Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China; Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, China; Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sheng
authors.affiliation: Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China.
authors.forename: Zhongfeng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Jia
authors.affiliation: Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Li
authors.affiliation: Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Fu
authors.affiliation: Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: An
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Lisi
authors.initials: L
authors.lastname: Sang
authors.affiliation: Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China.
authors.forename: Gongru
authors.initials: G
authors.lastname: Song
authors.affiliation: Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China; Central Laboratory, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Yanchuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China; Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, China; Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: qzhou@ioz.ac.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China. Electronic address: yaz@bjsap.org.
authors.forename: Y Alex
authors.initials: YA
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002454:Cell Differentiation; D002460:Cell Line; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D004742:Enhancer Elements, Genetic / Q000235:genetics; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064231:Nestin / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D010300:Parkinson Disease / Q000473:pathology / Q000628:therapy*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D060850:LIM-Homeodomain Proteins; C489692:Lmx1a protein, mouse; D064231:Nestin; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase