Conditionally Immortalized Neural Progenitor Cells Grafted to the Striatum Exhibit Site-Specific Neuronal Differentiation and Establish Connections with the Host Globus Pallidus

Abstract

The cell line RN33B has been reported to differentiate into neurons in a site-specific manner when grafted to the cortex and hippocampus of adult rats. To investigate the fate of RN33B cells in a subcortical structure, we grafted RN33B cells into the intact or excitoxically lesioned striatum of adult or neonatal rats. The total number and phenotypic characteristics of the [3H]thymidine-labeled grafted cells were analyzed at different time points after transplantation. Transplanted RN33B cells were found to survive, integrate, and differentiate into both neurons and astrocytes, and a significant proportion of the cells (approx. 10%) were found to differentiate into cells with morphological and phenotypic characteristics of medium-sized striatal projection neurons. Retrograde tracing showed that at least some of the graft-derived neurons were capable of establishing connections with one of the primary striatal targets, the globus pallidus. These findings demonstrate a remarkable capacity of the RN33B cells for site-specific neuronal differentiation in both the adult and the developing striatum and suggest that the same differentiating factors that are operating during normal neurogenesis in brain development are retained, at least to some extent, also in the adult CNS.