title: Spatiotemporal evolution of early innate immune responses triggered by neural stem cell grafting.
abstract: BACKGROUND
  Transplantation of neural stem cells (NSCs) is increasingly suggested to become part of future therapeutic approaches to improve functional outcome of various central nervous system disorders. However, recently it has become clear that only a small fraction of grafted NSCs display long-term survival in the (injured) adult mouse brain. Given the clinical invasiveness of NSC grafting into brain tissue, profound characterisation and understanding of early post-transplantation events is imperative to claim safety and efficacy of cell-based interventions.
  
  
  METHODS
  Here, we applied in vivo bioluminescence imaging (BLI) and post-mortem quantitative histological analysis to determine the localisation and survival of grafted NSCs at early time points post-transplantation.
  
  
  RESULTS
  An initial dramatic cell loss (up to 80% of grafted cells) due to apoptosis could be observed within the first 24 hours post-implantation, coinciding with a highly hypoxic NSC graft environment. Subsequently, strong spatiotemporal microglial and astroglial cell responses were initiated, which stabilised by day 5 post-implantation and remained present during the whole observation period. Moreover, the increase in astrocyte density was associated with a high degree of astroglial scarring within and surrounding the graft site. During the two-week follow up in this study, the NSC graft site underwent extensive remodelling with NSC graft survival further declining to around 1% of the initial number of grafted cells.
  
  
  CONCLUSIONS
  The present study quantitatively describes the early post-transplantation events following NSC grafting in the adult mouse brain and warrants that such intervention is directly associated with a high degree of cell loss, subsequently followed by strong glial cell responses.
authors.forename: Kristien
authors.initials: K
authors.lastname: Reekmans
authors.forename: Nathalie
authors.initials: N
authors.lastname: De Vocht
authors.forename: Jelle
authors.initials: J
authors.lastname: Praet
authors.forename: Erik
authors.initials: E
authors.lastname: Fransen
authors.forename: Debbie
authors.initials: D
authors.lastname: Le Blon
authors.forename: Chloé
authors.initials: C
authors.lastname: Hoornaert
authors.forename: Jasmijn
authors.initials: J
authors.lastname: Daans
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
authors.forename: Annemie
authors.initials: A
authors.lastname: Van der Linden
authors.forename: Zwi
authors.initials: Z
authors.lastname: Berneman
authors.forename: Peter
authors.initials: P
authors.lastname: Ponsaerts
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival; D002478:Cells, Cultured; D006085:Graft Survival; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D062211:Spatio-Temporal Analysis
chemical_list: D049452:Green Fluorescent Proteins