title: Comparative study on the therapeutic potential of neurally differentiated stem cells in a mouse model of multiple sclerosis.
abstract: BACKGROUND
  Transplantation of neural stem cells (NSCs) is a promising novel approach to the treatment of neuroinflammatory diseases such as multiple sclerosis (MS). NSCs can be derived from primary central nervous system (CNS) tissue or obtained by neural differentiation of embryonic stem (ES) cells, the latter having the advantage of readily providing an unlimited number of cells for therapeutic purposes. Using a mouse model of MS, we evaluated the therapeutic potential of NSCs derived from ES cells by two different neural differentiation protocols that utilized adherent culture conditions and compared their effect to primary NSCs derived from the subventricular zone (SVZ).
  
  
  RESULTS
  The proliferation and secretion of pro-inflammatory cytokines by antigen-stimulated splenocytes was reduced in the presence of SVZ-NSCs, while ES cell-derived NSCs exerted differential immunosuppressive effects. Surprisingly, intravenously injected NSCs displayed no significant therapeutic impact on clinical and pathological disease outcomes in mice with experimental autoimmune encephalomyelitis (EAE) induced by recombinant myelin oligodendrocyte glycoprotein, independent of the cell source. Studies tracking the biodistribution of transplanted ES cell-derived NSCs revealed that these cells were unable to traffic to the CNS or peripheral lymphoid tissues, consistent with the lack of cell surface homing molecules. Attenuation of peripheral immune responses could only be achieved through multiple high doses of NSCs administered intraperitoneally, which led to some neuroprotective effects within the CNS.
  
  
  CONCLUSIONS
  Systemic transplantation of these NSCs does not have a major influence on the clinical course of rMOG-induced EAE. Improving the efficiency at which NSCs home to inflammatory sites may enhance their therapeutic potential in this model of CNS autoimmunity.
authors.affiliation: Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, Victoria, Australia.
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Payne
authors.forename: Guizhi
authors.initials: G
authors.lastname: Sun
authors.forename: Daniella
authors.initials: D
authors.lastname: Herszfeld
authors.forename: Pollyanna A
authors.initials: PA
authors.lastname: Tat-Goh
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Verma
authors.forename: Helena C
authors.initials: HC
authors.lastname: Parkington
authors.forename: Harold A
authors.initials: HA
authors.lastname: Coleman
authors.forename: Mary A
authors.initials: MA
authors.lastname: Tonta
authors.forename: Christopher
authors.initials: C
authors.lastname: Siatskas
authors.forename: Claude C A
authors.initials: CC
authors.lastname: Bernard
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000628:therapy; D051379:Mice; D009103:Multiple Sclerosis / Q000628:therapy*; D009185:Myelin Proteins / Q000633:toxicity; D063308:Myelin-Oligodendrocyte Glycoprotein; D058953:Neural Stem Cells / Q000166:cytology* / Q000637:transplantation
chemical_list: C571327:Mog protein, mouse; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein