The developing human central nervous system (CNS) consists of pleuripotent cells which mature into astrocytes, oligodendrocytes and neurons. We have begun examining fetal brain from different gestational ages to determine at which gestational age differentiated cells can be identified. The constituent elements of the developing CNS can be separated from one another by a mechanical method allowing study of individual cellular components. This also allows the production of highly purified cultures of fetal neurons or astrocytes which can be used in cell culture models of HIV~1 or other neurotrophic infections. These brain cell cultures can also be useful in testing transplantation protocols for therapy of neurodegenerative disorders. We have previously developed an immortalized fetal astrocyte line (SVG) and have implanted them into the basal ganglia of six rhesus monkeys. In the rhesus CNS, the SVG cells survived without rejection or induction of a graft versus host response. Furthermore, no tumor formation or changes from normal behavior were noted. These data demonstrate the survivability of an astrocyte cell line as a xenograft, and suggest that these cells could act as a drug delivery system if genetically modified. To this end, we have modified the SVG cells by insertion of a tyrosine hydroxylase gene construct. These cells, SVG~TH, could potentially serve as an alternative to neural rafts of primary tissue in transplantation studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002852-02
Application #
3782436
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code