Neuroblastoma cells in neural transplants: a neuroanatomical and behavioral analysis.

The present experiments were aimed to determine the extent to which differentiated neuroblastoma cells may serve as a donor source for neural transplantation studies. Rodent-derived C1300 and human-derived LA-N-2 cells stained positively for choline acetyltransferase in vitro whether left untreated or rendered amitotic with mitomycin C/bromodeoxyuridine (Brdu) treatment. The two cell lines in both mitotic and differentiated states were subsequently transplanted into the hippocampus of rats that had previously undergone posterodorsal medial septal lesions. The undifferentiated cells continued to proliferate and formed large masses in the host brain within 7 days after implantation. When differentiated with mitomycin C/Brdu, the cells were autoradiographically visualized in large numbers 7 days following transplantation. Fewer cells were observed at the 30 and 120 test intervals. At the later time points the C1300 cells were found primarily within the host parenchyma while the LA-N-2 cells were found predominantly in the subependymal region below the hippocampus. These differentiated cells were also able to attenuate the cognitive dysfunction produced by medial septal lesions. However, an exact neurochemical mechanism cannot presently be ascribed to this effect since the cells failed to stain for choline acetyltransferase in vivo. At no time did differentiated cell grafts appear to revert to a neoplastic state nor was a significant immunological response observed. These findings, in concordance with other studies by our group, suggest that neuroblastoma cell lines may prove to be a practical source of donor tissue for neural transplants.