Multipotential marrow stromal cells transduced to produce L-DOPA: engraftment in a rat model of Parkinson disease.

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Schwarz EJ, Alexander GM, Prockop DJ, Azizi SA

Multipotential marrow stromal cells transduced to produce L-DOPA: engraftment in a rat model of Parkinson disease.

Hum Gene Ther. 1999 Oct 10;10(15):2539-49.

PubMed ID

10543618 [ View in PubMed

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Abstract

Bone marrow stromal cells can be used as an alternative source of cells for neural transplantation and repair. Here, the efficacy of genetically modified marrow stromal cells was examined in a rat model of Parkinson disease. Rat marrow stromal cells (rMSCs) and human marrow stromal cells (hMSCs) were genetically engineered by transduction with retroviruses encoding tyrosine hydroxylase (TH) and GTP cyclohydrolase I, the enzyme necessary for production of the tetrahydrobiopterin cofactor for TH (BH4). Transduced cells synthesized 3,4-dihydroxyphenylalanine (L-DOPA) in vitro and maintained their multipotentiality after retroviral transduction. To examine the cells in vivo, transduced rMSCs were injected into the striatum of 6-hydroxydopamine-lesioned rats. L-DOPA and metabolites were detected by microdialysis in the denervated striatum of rats that received doubly transduced rMSCs. Also, there was a significant reduction in apomorphine-induced rotation when compared with controls. The cells engrafted and survived for at least 87 days. However, expression of the transgenes ceased at about 9 days, an observation consistent with reports from other laboratories in which similar retroviruses were used to express transgenes in the brain.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Sapropterin	Tyrosine 3-monooxygenase	Protein	Humans	Yes	Cofactor	Details