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微囊化转TH基因人成纤维细胞脑内移植治疗帕金森病大鼠模型的研究 |
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戴晓玲 张进禄 徐群渊 赵春礼 赵焕英 孙晓红 郑少鹏
【摘要】 目的 探讨微囊化转酪氨酸羟化酶(TH)基因的细胞在帕金森病(PD)大鼠模型脑内存活、组织反应及对异常行为的治疗效果。 方法 以人TH基因作为目的基因，重组到逆转录病毒载体感染人成纤维细胞，将细胞包裹在APA半透膜中进行微囊化后，植入6-羟多巴胺单侧损毁的PD大鼠模型纹状体内，观察移植物的存活状况和功能作用16周。 结果 体外和植入体内的微囊化转基因细胞具有良好的存活能力。移植微囊化细胞可以使大鼠异常运动明显改善，移植位点周围的免疫反应较小。 结论 微囊化对转基因细胞异种移植以进行基因治疗具有显著意义。
【关键词】 帕金森病；基因治疗；酪氨酸羟化酶；人成纤维细胞；微囊；大鼠
【中图分类号】 R74.25 【文献标识码】 A 【文章编号】 0529-1356(2000)04-317
AN EXPERIMENTAL STUDY ON GENE THERAPY WITH
INTRACEREBRAL TRANSPLANTATION OF MICROCAPSULATED
HUMAN FIBROBLASTS EXPRESSING TH GENE
IN RAT MODEL OF PARKINSON DISEASE
DAI Xiao-ling ZHANG Jin-lu XU Qun-yuan ZHAO Chun-li ZHAO Huan-ying SUN Xiao-hong ZHENG Shao-peng
（Beijing Institute for Neuroscience, Capital University of Medical Sciences, Beijing 100054, China）
【Abstract】 Objectives The aim of this study was to evaluate the survival of the grafts, their immune response from hostissue and improvement of the locomotion after the intracerebral transplantation of microcapsulated genetically modified cells in the rat model of Parkinson Disease(PD). Methods The human tyrosine hydroxylase(TH) gene was recombined into a retrovirus vector and the newly constructed vector was then transfected into primary cultured human fibroblasts in vitro.These human fibroblasts were microcapsulated by the alginate-polylysine-alginate(APA)semipermeable membrane. The rat model of PD was made by unilateral 6-OHDA injection in the midbrain. These microcapulated genetically modified human fibroblasts were transplanted into the brain of the rat models. Results The microcapsulated cells could survive well in vivo at least 16 weeks. The grafting of these cells could induce a marked decrease in abnormal locomotion for the animal models and make a less immunorejection from host tissue. Conclusion The APA-microcapsulation may help gene therapy by use of xenograft with genetically modified cells.
【Key words】 Parkinson [1] [2] 下一页
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