Multipotential Marrow Stromal Cells Transduced to Produce L-DOPA: Engraftment in a Rat Model of Parkinson Disease

EJ Schwarz, GM Alexander, DJ Prockop… - Human gene …, 1999 - liebertpub.com
EJ Schwarz, GM Alexander, DJ Prockop, SA Azizi
Human gene therapy, 1999liebertpub.com
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 …
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.
Mary Ann Liebert