Genetically modified human embryonic stem cells relieve symptomatic motor behavior in a rat model of Parkinson's disease
Genetically modified human embryonic stem cells relieve symptomatic motor behavior in a rat model of Parkinson's disease
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转基因人类胚胎干细胞可缓解帕金森病大鼠模型的症状运动行为
DOI：
10.1016/j.neulet.2003.08.082
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发表时间：
2003
影响因子：
2.5
通讯作者：
Jin
中科院分区：
文献类型：
--
作者：
Se;Eun Young Kim;Gwang Su Ghil;W. Joo;K. Wang;Y. S. Kim;Young Jae Lee;Jin
胚胎干细胞作为细胞替代治疗的细胞来源具有很大的潜力。为探讨ES细胞作为治疗基因载体(S)的可能性，将编码酪氨酸羟基酶(TH)和GTP环水解酶I(GTPCH I)的基因共转染人ES细胞(MB03)，并在新霉素和潮霉素B存在下进行批量筛选。Western免疫印迹和RT-PCR检测证实成功。将转基因ES细胞(BK-THGC)移植到6-羟色胺去神经支配的大鼠脑纹状体内，自发产生大量的L-多巴，并可减轻阿朴吗啡诱导的不对称运动行为约54%。植入PBS后6周旋转次数增加176±18%(假手术组)。免疫组织化学染色显示，移植的人ES细胞存活并在实验继续期间表达TH至少6周。
Embryonic stem (ES) cells have great potential as a cell source for cell replacement therapy. To investigate the possibility of using ES cells as a carrier of therapeutic gene(s), human ES cells (MB03) were co-transfected with cDNAs coding for tyrosine hydroxylase (TH) and GTP cyclohydrolase I (GTPCH I), then bulk-selected in the presence of neomycin and hygromycin-B. Successful transfection was confirmed by Western immunoblotting and RT-PCR. The genetically modified ES cells (bk-THGC) were found to produce a significant amount of l-dopa spontaneously and relieved apomorphine-induced asymmetric motor behavior by approximately 54% when grafted into striatum of 6-OHDA-denervated rat brain. The number of rotations, however, increased up to 176±18% in 6 weeks when PBS was used instead (sham-graft). Immunohistochemical stainings revealed that the grafted human ES cells survived and expressed TH for at least 6 weeks while the experiment was continued.