Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease.

作者：Jon A. Wolff, L. J. Fisher, Li Xu, Hyder Azad Jinnah, P. J. Langlais, Paul Michael Iuvone, Karen L. O’Malley, Michael B. Rosenberg, Shun Shimohama, T Friedmann · 发表于：Proceedings of the National Academy of Sciences · 年份：1989 · DOI：10.1073/pnas.86.22.9011 · 被引用次数：256 · 研究领域：Pluripotent Stem Cells Research、Animal Genetics and Reproduction、Tissue Engineering and Regenerative Medicine

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.