Neurospheres and multipotent astrocytic stem cells: Neural progenitor cells rather than neural stem cells

Adult hematopoiesis is driven by the hematopoietic stem cell (HSC), a cell residing in the bone marrow that possesses unique, functional characteristics defining it as a true stem cell. Neural stem cells (NSCs) are reported to exist in the brains of adult mice in two well characterized regions: the subependymal zone (SEZ) of the lateral ventricles (LV) and the hippocampal dentate gyrus. Mitotic neuroblasts are continuously generated by the SEZ and migrate along the rostral migratory stream (RMS) toward the olfactory bulb, where they functionally integrate as interneurons. SEZ NSCs can be cultured under specific conditions to generate neurospheres (NS) or multipotent astrocytic stem cells (MASC), cell types that possess certain stem cell qualities in vitro. However, the in vivo stem cell characteristics possessed by cultured NSCs (specifically functional engraftment and serial transplantation) are not fully understood.; Green fluorescent protein (gfp) NS and MASC transplanted into the LV of both neonatal and adult C57BL/6 mice resulted in engraftment into the recipient brain, with donor-derived migratory neuroblasts visible in the RMS weeks after transplantation. Neither displayed the capacity to be re-isolated from adult or neonatal brains even under rigorous enrichment conditions, nor were they evident in the brains of secondary recipient mice, indicating that functional, long-term engraftment by the transplanted cells failed to occur.; Exposure of adult C57BL/6 mice to lethal levels of ionizing radiation resulted in the ablation of both active hematopoiesis and SEZ neurogenesis, with subsequent transplantation of gfp MASC into the LV resulting in no observable engraftment. Exposure to sublethal levels of radiation resulted in a transient depletion of SEZ neurogenesis and moderately enhanced engraftment levels of transplanted gfp+ MASC, potentially providing a more ideal model system for NSC transplantation and analysis.; In this study, both NS and MASC failed to meet the criteria of true stem cells as defined by the properties of the adult HSC. Thus it is possible that neurogenesis in the adult brain is provided not by an isolatable NSC but rather by neural progenitor cells derived from a migratory adult stem cell residing in the bone marrow.