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Xenografting of human umbilical mesenchymal stem cells from Wharton’s jelly ameliorates mouse spinocerebellar ataxia type 1

查看全文 作　　者：Pei-Jiun [1,2,3]Tsai;Chang-Ching [4,5,6]Yeh;Wan-Jhen [1]Huang;Ming-Yuan [7]Min;Tzu-Hao [1]Huang;Tsui-Ling [8]Ko;Pei-Yu [9]Huang;Tien-Hua [1,2,10]Chen;Sanford [11,12]P.C.Hsu;Bing-Wen [13,14,15]Soong;Yu-Show [16]Fu 高影响力作者 机构地区：[1]Institute of Anatomy and Cell Biology,School of Medicine,National Yang-Ming University,Taipei,Taiwan,Republic of China;[2]Trauma Center,Department of Surgery,Veterans General Hospital,Taipei,Taiwan,Republic of China;[3]Department of Critical Care Medicine,Veterans General Hospital,Taipei,Taiwan,Republic of China;[4]Department of Obstetrics and Gynecology,Veterans General Hospital,Taipei,Taiwan,Republic of China;[5]Institute of Clinical Medicine,National Yang-Ming University,Taipei,Taiwan,Republic of China;[6]Department of Obstetrics and Gynecology,National Yang-Ming University,Taipei,Taiwan,Republic of China;[7]Department of Life Science,National Taiwan University,Taipei,Taiwan,Republic of China;[8]School of Medicine,I-Shou University,Kaohsiung,Taiwan,Republic of China;[9]Institute of Physiology,School of Medicine,National Yang-Ming University,Taipei,Taiwan,Republic of China;[10]Division of General Surgery,Department of Surgery,Veterans General Hospital,Taipei,Taiwan,Republic of China;[11]Department of Neurosurgery,Neurological Institute,Taipei Veterans General Hospital,Taipei,Taiwan,Republic of China;[12]School of Medicine,National Yang-Ming University,Taipei,Taiwan,Republic of China;[13]Department of Neurology,Shuang Ho Hospital,and Taipei Neuroscience Institute,Taipei Medical University,Taipei,Taiwan,Republic of China;[14]Department of Neurology,Taipei Veterans General Hospital,Taipei,Taiwan,Republic of China;[15]Brain Research Center,National Yang-Ming University,Taipei,Taiwan,Republic of China;[16]Department of Anatomy and Cell Biology,School of Medicine,National Yang-Ming University,No.155,Sec.2,Li-Nung Street,Taipei 112,Taiwan,Republic of China高影响力机构 出　　处：《Translational Neurodegeneration》索引2019年第8卷第1期,共13页高影响力期刊 基　　金：This work was supported by grants from the Ministry of Science and Technology,Taiwan(MOST 103-2314-B-075-032-MY2,MOST 103-2314-B-010-049-MY3,MOST 104-2320-B-010-013,MOST 107-2321-B-010-003 and MOST 107-2314-B-010-017);Taipei Veterans General Hospital(V103C-098 and V104C-035);the Yin Yen-Liang Foundation Development and Construction Plan of the School of Medicine,National Yang-Ming University(107F-M01);the Higher Education Sprout Project by the Ministry of Education(MOE)in Taiwan,as well as the research funds from the Taiwan Ataxia Association and the Hsu Tsung Pei Medical Research Fund. 摘　　要：Background:Spinocerebellar ataxia type 1(SCA1)is an autosomal dominant neurodegenerative disorder caused by the expansion of CAG repeats in ATXN1 gene resulting in an expansion of polyglutamine repeats in the ATXN1 protein.Unfortunately,there has yet been any effective treatment so far for SCA1.This study investigated the feasibility of transplanting human umbilical mesenchymal stem cells(HUMSCs)into transgenic SCA1 mice containing an expanded uninterrupted allele with 82 repeats in the ATXN1-coding region.Methods:106 human umbilical mesenchymal stem cells were transplanted into the cerebella at 1 month of age.Results:HUMSCs displayed significant ameliorating effects in SCA1 mice in terms of motor behaviors in balance beam test and open field test as compared with the untransplanted SCA1 mice.HUMSCs transplantation effectively reduced the cerebellar atrophy,salvaged Purkinje cell death,and alleviated molecular layer shrinkage.Electrophysiological studies showed higher amplitudes of compound motor action potentials as indicated by increasing neuronal-muscular response strength to stimuli after stem cell transplantation.At 5 months after transplantation,HUMSCs scattering in the mice cerebella remained viable and secreted cytokines without differentiating into neuronal or glia cells.Conclusions:Our findings provide hope for a new therapeutic direction for the treatment of SCA1. 关 键 词：Umbilical mesenchymal stem cells Cell transplantation SCA1
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