微囊化转基因肌细胞治疗帕金森病大鼠模型的实验研究

AN EXPERIMENTAL STUDY ON GENE THERAPY OF PARKINSONISM BY TRANSPLANTATION OF MICROCAPSULATED TH-EXPRESSING MUSCLE CELLS

为了探讨微囊化转酪氨酸羟化酶基因的细胞在帕金森病大鼠模型脑内存活、组织反应及对异常行为的治疗效果。本研究将带有酪氨酸羟化酶基因的载体—质粒 p CMV-TH在体外通过脂质体转染技术转入原代培养的人胚骨骼肌细胞内。将转染后的肌细胞包裹在藻酸盐 -多聚赖氨酸 -藻酸盐构成的半透膜微囊中 ,然后将这些微囊化的能表达酪氨酸羟化酶的骨骼肌细胞植入模型大鼠脑的纹状体内。结果表明 ,微囊化的转基因细胞在脑内可存活至实验结束 (16周 ) ,可表达酪氨酸羟化酶。微囊化细胞周围无显著免疫排斥反应及炎症反应。本研究结果表明

The aim of this study was to evaluate the survival of the microcapsulated cells in the brain, their therapeutic effects and the immune responses against them from the host tissue, after they were intracerebrally grafted into the striatum of the rat model of Parkinson's disease. The microcapsulated cells used in the present study were the genetically modified muscle cells expressing tyrosine hydroxylase (TH) from human fetus. The plasmid, pCMV-TH contains TH gene, was transfected into those muscle cells ex vivo by lipofectin. The genetically modified cells expressing TH gene were enclosed within the microcapsules which were made from alginate-polylysine-alginate (APA) in vitro before implantation. The results showed that these microcapsulated TH-expressing cells survived well and expressed TH positively in vivo till the end of the study (16 weeks). There was no apparent immune rejection and inflammatory response from the host tissue. This study indicated that microcapsulation of gene altered cells was an effective and applicable way for gene therapy by using xenografting.