Characterization of a CNS-derived neuroepithelial precursor cell line following transplantation into the intact and injured CNS
Date of Award
Doctor of Philosophy (Ph.D.)
First Committee Member
Scott Whittemore, Committee Chair
The developmental capacity of the conditionally immortalize neuroepithelial cell line, RN33B, was examined following transplantation into the intact and lesioned CNS. Following transplantation into the adult and neonate cerebral cortex and hippocampus, stably integrated RN33B cells with various morphologies consistent with their transplantation site were seen up to 24 weeks post-transplantation. In the cerebral cortex, many RN33B cells differentiated with morphologies similar to pyramidal neurons and stellate cells. In the hippocampal formation, many RN33B cells assumed morphologies similar to pyramidal neurons characteristic of CA1 and CA3 regions, granular cell layer neurons of the dentate gyrus, and polymorphic neurons of the hilar region. Immunohistochemical evaluation of the transplanted RN33B cells demonstrated that some differentiated RN33B cells expressed a region-specific neuronal marker and exhibited glutamate immunoreactivity. Ultrastructural evaluation revealed that host axons made synaptic contact with the transplanted RN33B cells in both hippocampus and cerebral cortex. These results suggest that both adult and neonatal CNS retain the capacity to direct the differentiation of neuronal precursor cells in a direction that is consistent with that of endogenous neurons and that RN33B cells are capable of region-specific differentiation and have the potential to integrate functionally into the host CNS. Following chemical ablation of endogenous hippocampal pyramidal or granule neurons, transplanted RN33B cells did not similarly differentiate and became bipolar. Only RN33B cells located in layers with some spared endogenous neurons differentiated with appropriate neuronal phenotypes. The requirement for close apposition of transplanted RN33B cells to endogenous neurons suggest that cell-cell interaction may be essential for these immortalized neuroepithelial precursor cells to differentiate into region-specific neuronal cell types.
Biology, Neuroscience; Biology, Cell
Shihabuddin, Lamya Sami, "Characterization of a CNS-derived neuroepithelial precursor cell line following transplantation into the intact and injured CNS" (1995). Dissertations from ProQuest. 3383.