POLYMER-ENCAPSULATED SCHWANNOMA CELLS EXPRESSING HUMAN NERVE GROWTH-FACTOR PROMOTE THE SURVIVAL OF CHOLINERGIC NEURONS AFTER A FIMBRIA-FORNIX TRANSECTION

Many investigators have recently used genetically modified primary fib roblasts of fibroblast cell lines (e.g., 3T3, 208F, or BHK cells) to d eliver recombinant nerve growth factor (NGF) into the CNS. In the curr ent study, SCT-1 cells, a Schwannoma cell line derived from a transgen ic mouse, were transfected with a human NGF (hNGF) cDNA. After selecti on, these cells were encased within a polymer capsule and implanted in to the ventricles of fimbria-fornix lesioned rats. Encapsulated, non-t ransfected cells served as controls. Results demonstrated that the hNG F transgene is expressed for at least 3 weeks after implantation. More over, the cells did not overgrow the capsule. Recombinant hNGF was abl e to save >70% of lesioned cholinergic neurons, as assessed by NGF-rec eptor (NGFr) and choline acetyltransferase (ChAT) immunohistochemistry , from cell death. The number of cholinergic neurons in animals that r eceived control capsules (i.e., nontransfected SCT-I cells) was simila r to lesion only animals (i.e., similar to 27% and similar to 33% for NGFr- and ChAT-positive neurons, respectively. These results show that SCT-1 cells can be used to deliver biologically active hNGF into the lesioned rat brain.