Genetically modified PC12 brain grafts: Survivability and inducible nerve growth factor expression

D. C. Rohrer, G. Nilaver, V. Nipper, C. A. Machida

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)57-68
Number of pages12
JournalCell Transplantation
Volume5
Issue number1
DOIs
StatePublished - Jan 1 1996

Keywords

  • Brain grafts
  • Nerve growth factor
  • Neural transplantation
  • Parkinson's disease

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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