Genetically Modified Pc 12 Brain Grafts: Survivability and Inducible Nerve Growth Factor Expression

Cell Transplantation

Original Contribution

Gajanan Nilaver¹  Curtis A. Machida²  Valerie Nipper³  Daniel C. Rohrer⁴ 

[1]Departments of Neurology Oregon Health Sciences University, Portland, OR 97201 USA

[2]Departments of Cell and Developmental Biology, and Graduate Programs Oregon Health Sciences University, Portland, OR 97201 USA

[3]Departments of Neuroscience Oregon Health Sciences University, Portland, OR 97201 USA

[4]Departments of Molecular and Cell Biology, Oregon Health Sciences University, Portland, OR 97201 USA

[5]Division of Neuroscience, Oregon Regional Primate Research Center, Oregon Health Sciences University, Beaverton, Oregon 97006 USA

[6]Division of Neuroscience, Oregon Regional Primate Research Center, Oregon Health Sciences University, Beaverton, Oregon 97006 USA

[7]Division of Neurosurgery, Oregon Health Sciences University, Portland, OR 97201 USA

关键词: Brain grafts;    Neural transplantation;    Nerve growth factor;    Parkinson's disease;   

DOI  :  10.1177/096368979600500111

来源: Sage Journals

【 摘 要 】

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 neurodifferentiate, 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.

【 授权许可】

Unknown   
© 1996 Elsevier Science Inc.