Delivery of Nerve Growth Factor Within the Rat Brain Using Genetically Modified Cells

Author(s):  
M. D. Kawaja ◽  
F. H. Gage
1996 ◽  
Vol 728 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Marius C. Hoener ◽  
Eleanore Hewitt ◽  
James M. Conner ◽  
James W. Costello ◽  
Silvio Varon

1991 ◽  
Vol 9 (4) ◽  
pp. 319-325 ◽  
Author(s):  
Lucio Cavicchioli ◽  
Thomas P. Flanigan ◽  
John G. Dickson ◽  
Guido Vantini ◽  
Roberto Dal Toso ◽  
...  

1993 ◽  
Vol 632 (1-2) ◽  
pp. 57-67 ◽  
Author(s):  
Z.-C. Peng ◽  
S. Chen ◽  
M. Fusco ◽  
G. Vantini ◽  
M. Bentivoglio

1996 ◽  
Vol 5 (1) ◽  
pp. 57-68
Author(s):  
Daniel C. Rohrer ◽  
Gajanan Nilaver ◽  
Valerie Nipper ◽  
Curtis A. Machida

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.


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