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Intracerebral grafting is a new strategy of the treatment for Parkison's disease. We focused on primary skin fibroblasts for the grafts. Rat primary skin fibroblasts were transfected with a retrovirus vector (PLTHSNL) containing the cDNA of human tyrosine hydroxylase (TH). Catecholamine released from these genetically modified fibroblasts were measured by high performance liquid chromatography with electrochemical detection (HPLC-ECD) analysis. When supplemented with biopterin (BH4:(6R)-L-erythro-tetrahydrobiopterin), a co factor required for TH activity, these cells produced and released L-DOPA into the culture medium. The data suggest that production of L-DOPA from genetically modified fibroblasts can be regulated by biopterin. The ability of L-DOPA production was not affected by the number of cell-passages and freezes. Because retrovirus vector containing the foreign gene (THcDNA) is integrated into chromosomal DNA of the target cells (fibroblasts), the gene is stable. Primary skin fibroblasts can be obtained and cultured easily. And these cells did not become tumors by transfection with a retrovirus vector. It was suggested that genetically modified primary skin fibroblasts transfected with THcDNA using retrovirus vector system is a worthy graft for transplantation and gene therapy in Parkinson's disease., 論文