title: Human neural progenitor cell engraftment increases neurogenesis and microglial recruitment in the brain of rats with stroke.
abstract: OBJECTIVE
  Stem cell transplantation is to date one of the most promising therapies for chronic ischemic stroke. The human conditionally immortalised neural stem cell line, CTX0E03, has demonstrable efficacy in a rodent model of stroke and is currently in clinical trials. Nonetheless, the mechanisms by which it promotes brain repair are not fully characterised. This study investigated the cellular events occurring after CTX0E03 transplantation in the brains of rats that underwent ischemic stroke.
  
  
  METHODS
  We focused on the endogenous proliferative activity of the host brain in response to cell transplantation and determined the identity of the proliferating cells using markers for young neurons (doublecortin, Dcx) and microglia (CD11b). So as to determine the chronology of events occurring post-transplantation, we analysed the engrafted brains one week and four weeks post-transplantation.
  
  
  RESULTS
  We observed a significantly greater endogenous proliferation in the striatum of ischemic brains receiving a CTX0E03 graft compared to vehicle-treated ischemic brains. A significant proportion of these proliferative cells were found to be Dcx+ striatal neuroblasts. Further, we describe an enhanced immune response after CTX0E03 engraftment, as shown by a significant increase of proliferating CD11b+ microglial cells.
  
  
  CONCLUSIONS
  Our study demonstrates that few Dcx+ neuroblasts are proliferative in normal conditions, and that this population of proliferative neuroblasts is increased in response to stroke. We further show that CTX0E03 transplantation after stroke leads to the maintenance of this proliferative activity. Interestingly, the preservation of neuronal proliferative activity upon CTX0E03 transplantation is preceded and accompanied by a high rate of proliferating microglia. Our study suggests that microglia might mediate in part the effect of CTX0E03 transplantation on neuronal proliferation in ischemic stroke conditions.
authors.affiliation: Centre for the Cellular Basis of Behaviour, The James Black Centre, King's College London, Institute of Psychiatry, London, United Kingdom.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hassani
authors.forename: Joanna
authors.initials: J
authors.lastname: O'Reilly
authors.forename: Yewande
authors.initials: Y
authors.lastname: Pearse
authors.forename: Paul
authors.initials: P
authors.lastname: Stroemer
authors.forename: Ellen
authors.initials: E
authors.lastname: Tang
authors.forename: John
authors.initials: J
authors.lastname: Sinden
authors.forename: Jack
authors.initials: J
authors.lastname: Price
authors.forename: Sandrine
authors.initials: S
authors.lastname: Thuret
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D039481:CD11b Antigen / Q000096:biosynthesis; D002461:Cell Line, Transformed; D002465:Cell Movement; D049109:Cell Proliferation; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006801:Humans; D008297:Male; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000096:biosynthesis; D051381:Rats; D020521:Stroke / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014183:Transplantation, Heterologous
chemical_list: D015415:Biomarkers; D039481:CD11b Antigen; C000714328:DCX protein, human; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides