Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease.
Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease.
复制标题
DOI：
10.1073/pnas.86.22.9011
复制
发表时间：
1989-11
影响因子：
11.1
通讯作者：
J. Wolff;Lisa J. Fishers;Li Xu;Hyder A. JINNAHt;Philip J. LANGLAISt;P. M. Iuvoneii;K. O’Malley;M. B. Rosenberg;Shun SHIMOHAMAt;Théodore;Friedmann;Fred H. GAGEttt
中科院分区：
文献类型：
--
作者：
J. Wolff;Lisa J. Fishers;Li Xu;Hyder A. JINNAHt;Philip J. LANGLAISt;P. M. Iuvoneii;K. O’Malley;M. B. Rosenberg;Shun SHIMOHAMAt;Théodore;Friedmann;Fred H. GAGEttt
大鼠成纤维细胞被含有大鼠酪氨酸羟化酶[TH; cDNA]的逆转录病毒载体感染。酪氨酸3-单加氧酶； L-酪氨酸，四氢蝶啶：氧氧化还原酶（3-羟基化），EC 1.14.16.2]。通过生化测定和免疫组织化学染色鉴定出 TH 阳性克隆。当在体外补充 TH 活性所需的蝶呤辅助因子时，这些细胞产生左旋多巴并将其释放到细胞培养基中。将未感染的对照细胞和感染TH载体的成纤维细胞分别移植到黑质纹状体通路单侧6-羟基多巴胺损伤的大鼠尾状核上。仅含有表达 TH 的成纤维细胞的移植物被发现可以减少旋转不对称性。这些结果对于基因疗法在人类神经系统疾病中的应用具有一般意义，对帕金森病具有特殊意义。
Rat fibroblasts were infected with a retroviral vector containing the cDNA for rat tyrosine hydroxylase [TH; tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2]. A TH-positive clone was identified by biochemical assay and immunohistochemical staining. When supplemented in vitro with pterin cofactors required for TH activity, these cells produced L-dopa and released it into the cell culture medium. Uninfected control cells and fibroblasts infected with the TH vector were grafted separately to the caudate of rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway. Only grafts containing TH-expressing fibroblasts were found to reduce rotational asymmetry. These results have general implications for the application of gene therapy to human neurological disease and specific implications for Parkinson disease.