title: Ionizing radiation enhances the engraftment of transplanted in vitro-derived multipotent astrocytic stem cells.
abstract: The subependymal zone (SEZ) is a region of persistent neurogenesis in the adult mammalian brain containing a neural stem cell (NSC) pool that continuously generates migratory neuroblasts that travel in chains through the rostral migratory stream (RMS) to the olfactory bulb (OB), where they differentiate and functionally integrate into existing neural circuitry. NSCs can be isolated from the SEZ and cultured to generate either neurospheres (NSs) or multipotent astrocytic stem cells (MASCs), with both possessing the stem cell characteristics of multipotency and self-renewal. NSs and MASCs home to the SEZ after transplantation into the lateral ventricle (LV) and contribute to neuroblast migration, with minimal engraftment into the OB observed in the adult mouse. Recent studies have compared the relatively uncharacterized NSC with the more established hematopoietic stem cell (HSC) in an effort to determine the level of stemness possessed by the NSC. Depletion of native HSCs in the bone marrow by lethal irradiation (LI) is necessary to maximize functional engraftment of donor HSCs. Our data show that the NSC pool and neuroblasts in the SEZ can be significantly and permanently depleted by exposure to LI. Attenuation of donor-derived migratory neuroblast engraftment into the OB is observed after transplantation of gfp+ MASCs into the LV of LI animals, whereas engraftment is significantly enhanced after transplantation into animals exposed to sublethal levels of ionizing radiation. By increasing receptiveness of the NSC niche through depletion of indigenous cells, the adult SEZ-RMS-OB can be used as a model to further characterize the NSC.
authors.affiliation: Program in Stem Cell Biology and Regenerative Medicine, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32611, USA. gpm2@ufl.edu
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Marshall
authors.forename: Edward W
authors.initials: EW
authors.lastname: Scott
authors.forename: Tong
authors.initials: T
authors.lastname: Zheng
authors.forename: Eric D
authors.initials: ED
authors.lastname: Laywell
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Steindler
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects* / Q000637:transplantation*; D048708:Cell Growth Processes / Q000528:radiation effects; D002465:Cell Movement / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D005260:Female; D006085:Graft Survival / Q000528:radiation effects; D020547:Lateral Ventricles / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D016548:Prosencephalon / Q000166:cytology; D033581:Stem Cell Transplantation