Stem cell transplantation and/or adenoviral glial cell line-derived neurotrophic factor promote functional recovery in hemiparkinsonian rats  

作　　者：May-Jywan Tsai Shih-Chieh Hung Ching-Feng Weng Su-Fen Fan Dann-Ying Liou Wen-Cheng Huang Kang-Du Liu Henrich Cheng 

机构地区：[1]Department of Neurosurgery,Neurological Institute,Neurological Institute,Taipei 11217,Taiwan [2]Department of Medical Research,National Yang Ming University,Institute of Clinical Medicine,Taipei 112,Taiwan [3]Integrative Stem Cell Center,Department of Orthopaedics,China Medical University Hospital,Taichung 404,Taiwan [4]Institute of Biomedical Sciences,Academia Sinica,Taipei 11529,Taiwan [5]China Medical University,Graduate Institute of Clinical Medical Sciences,Taichung 404,Taiwan [6]Department of Medical Research and Education,Taipei Veterans General Hospital,Stem Cell Laboratory,Taipei 112,Taiwan [7]Department of Life Science,Institute of Biotechnology,Haulien 97401,Taiwan [8]Department of Neurosurgery,Neurological Institute,Taipei 112,Taiwan [9]School of Medicine,National Yang-Ming University,Taipei 112,Taiwan [10]Department of neurosurgery,Neurological Institute,Taipei 112,Taiwan [11]Department of Neurosurgery,Taipei Veterans General Hospital,Center for Neural Regeneration,Neurological Institute,Taipei 112,Taiwan

出　　处：《World Journal of Stem Cells》2021年第1期78-90,共13页世界干细胞杂志（英文版）（电子版）

基　　金：Supported by Taipei Veterans General Hospital in Taiwan,No.V106C-012,No.V107C-087,and No.V109C-018;and Ministry of Science and Technology in Taiwan,No.MOST106-2314-B-075-023,No.MOST107-2314-B-010-023,and No.MOST107-2314-B-075-021.

摘　　要：BACKGROUND Parkinson’s disease(PD)is a neurological disorder characterized by the progressive loss of midbrain dopamine(DA)neurons.Bone marrow mesenchymal stem cells(BMSCs)can differentiate into multiple cell types including neurons and glia.Transplantation of BMSCs is regarded as a potential approach for promoting neural regeneration.Glial cell line-derived neurotrophic factor(GDNF)can induce BMSC differentiation into neuron-like cells.This work evaluated the efficacy of nigral grafts of human BMSCs(hMSCs)and/or adenoviral(Ad)GDNF gene transfer in 6-hydroxydopamine(6-OHDA)-lesioned hemiparkinsonian rats.AIM To evaluate the efficacy of nigral grafts of hMSCs and/or Ad-GDNF gene transfer in 6-OHDA-lesioned hemiparkinsonian rats.METHODS We used immortalized hMSCs,which retain their potential for neuronal differentiation.hMSCs,preinduced hMSCs,or Ad-GDNF effectively enhanced neuronal connections in cultured neurons.In vivo,preinduced hMSCs and/or Ad-GDNF were injected into the substantia nigra(SN)after induction of a unilateral 6-OHDA lesion in the nigrostriatal pathway.RESULTS Hemiparkinsonian rats that received preinduced hMSC graft and/or Ad-GDNF showed significant recovery of apomorphine-induced rotational behavior and the number of nigral DA neurons.However,DA levels in the striatum were not restored by these therapeutic treatments.Grafted hMSCs might reconstitute a niche to support tissue repair rather than contribute to the generation of new neurons in the injured SN.CONCLUSION The results suggest that preinduced hMSC grafts exert a regenerative effect and may have the potential to improve clinical outcome.

关 键 词：Stem cells TRANSPLANTATION Parkinson’s disease Glial cell line-derived neurotrophic factor ADENOVIRUS NEUROREGENERATION 

分 类 号：R742.5[医药卫生—神经病学与精神病学]