机构:[a]Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China首都医科大学宣武医院[b]Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China[c]Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, China[d]Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China[e]State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China[f]Central Laboratory, Xuanwu Hospital, Capital Medical University, Beijing 100053, China首都医科大学宣武医院[g]Institute of Reconstructive Neurobiology, University of Bonn, Sigmund-Freud-Straβe 25, D-53127 Bonn, Germany.
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 11 weeks 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. (C) 2014 The Authors. Published by Elsevier B.V.
基金:
National Basic Research Program of China [2012CBA01307, 2011CB965103]; National Natural Science Foundation of China [31340075, 31070946, 81141014, 81422014]; Beijing Municipal Natural Science Foundation [5142005]
第一作者机构:[a]Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China[b]Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China[c]Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, China[d]Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
共同第一作者:
通讯作者:
通讯机构:[*1]The State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences,1 Beichen West Road, Chaoyang District, Beijing 100101, China.[*2]Cell therapy center, Xuanwu Hospital, 45 Changchun Street, Xicheng District, Beijing 100053, China.
推荐引用方式(GB/T 7714):
Jianyu Wu,Chao Sheng,Zhongfeng Liu,et al.Lmx1a enhances the effect of iNSCs in a PD model[J].STEM CELL RESEARCH.2015,14(1):1-9.doi:10.1016/j.scr.2014.10.004.
APA:
Jianyu Wu,Chao Sheng,Zhongfeng Liu,Weili Jia,Bin Wang...&Y. Alex Zhang.(2015).Lmx1a enhances the effect of iNSCs in a PD model.STEM CELL RESEARCH,14,(1)
MLA:
Jianyu Wu,et al."Lmx1a enhances the effect of iNSCs in a PD model".STEM CELL RESEARCH 14..1(2015):1-9