Genetically modified PC12 brain grafts: survivability and inducible nerve growth factor expression.
Neural transplantation of genetically modified cells has been successfully employed to reverse functional deficits in animal models of neurodegenerative disorders, including Parkinson's disease. While implanted PC12 cells secrete dopamine in vivo and can ameliorate dopamine deficiency in parkinsonian rat model systems, these cells either degenerate within 2-3 wk postimplantation (presumably due to the lack of neural trophic factor support at the site of implantation), or in some cases, form a tumor mass leading to the death of the host animal. To address these limitations, we have developed a genetically modified PC12 cell line that can synthesize nerve growth factor (NGF) under the control of a zinc-inducible metallothionein promoter. When implanted in the rat striatum and under in vivo zinc stimulation, these cells will neuro-differentiate, express tyrosine hydroxylase, and will undergo survival through potential autocrine trophic support. This regulatable cell line and general approach may provide additional insight on the potential utilization of cell transplants for treatment of Parkinson's disease and other neurodegenerative disorders.
Rohrer
D C
DC
Division of Neuroscience, Oregon Health Sciences University, Beaverton 97006, USA.
Nilaver
G
G
Nipper
V
V
Machida
C A
CA
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D015870:Gene Expression; D006085:Graft Survival; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation / Q000502:physiology*; D009414:Nerve Growth Factors / Q000032:analysis / Q000096:biosynthesis*; D016716:PC12 Cells; D010302:Parkinson Disease, Secondary / Q000628:therapy*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis; D014158:Transcription, Genetic; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000096:biosynthesis
D017931:DNA Primers; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014446:Tyrosine 3-Monooxygenase