title: Intravenous administration of human embryonic stem cell-derived neural precursor cells attenuates cuprizone-induced central nervous system (CNS) demyelination.
abstract: OBJECTIVE
  Previous studies have demonstrated the therapeutic potential for human embryonic stem cell-derived neural precursor cells (hES-NPCs) in autoimmune and genetic animal models of demyelinating diseases. Herein, we tested whether intravenous (i.v.) administration of hES-NPCs would impact central nervous system (CNS) demyelination in a cuprizone model of demyelination.
  
  
  METHODS
  C57Bl/6 mice were fed cuprizone (0.2%) for 2 weeks and then separated into two groups that either received an i.v. injection of hES-NPCs or i.v. administration of media without these cells. After an additional 2 weeks of dietary cuprizone treatment, CNS tissues were analysed for detection of transplanted cells and differences in myelination in the region of the corpus callosum (CC).
  
  
  RESULTS
  Cuprizone-induced demyelination in the CC was significantly reduced in mice treated with hES-NPCs compared with cuprizone-treated controls that did not receive stem cells. hES-NPCs were identified within the brain tissues of treated mice and revealed migration of transplanted cells into the CNS. A limited number of human cells were found to express the mature oligodendrocyte marker, O1, or the astrocyte marker, glial fibrillary acidic protein. Reduced apoptosis and attenuated microglial and astrocytic responses were also observed in the CC of hES-NPC-treated mice.
  
  
  CONCLUSIONS
  These findings indicated that systemically administered hES-NPCs migrated from circulation into a demyelinated lesion within the CNS and effectively reduced demyelination. Observed reductions in astrocyte and microglial responses, and the benefit of hES-NPC treatment in this model of myelin injury was not obviously accountable to tissue replacement by exogenously administered cells.
authors.affiliation: Department of Neuroscience, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USA. crocker@uchc.edu
authors.forename: S J
authors.initials: SJ
authors.lastname: Crocker
authors.forename: R
authors.initials: R
authors.lastname: Bajpai
authors.forename: C S
authors.initials: CS
authors.lastname: Moore
authors.forename: R F
authors.initials: RF
authors.lastname: Frausto
authors.forename: G D
authors.initials: GD
authors.lastname: Brown
authors.forename: R R
authors.initials: RR
authors.lastname: Pagarigan
authors.forename: J L
authors.initials: JL
authors.lastname: Whitton
authors.forename: A V
authors.initials: AV
authors.lastname: Terskikh
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D003337:Corpus Callosum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D003471:Cuprizone / Q000494:pharmacology*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D051379:Mice; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D058953:Neural Stem Cells; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
chemical_list: D003471:Cuprizone