Document Detail

Signaling through three chemokine receptors triggers the migration of transplanted neural precursor cells in a model of multiple sclerosis.
MedLine Citation:
PMID:  25086214     Owner:  NLM     Status:  Publisher    
Multiple sclerosis (MS) is a multifocal disease, and precursor cells need to migrate into the multiple lesions in order to exert their therapeutic effects. Therefore, cell migration is a crucial element in regenerative processes in MS, dictating the route of delivery, when cell transplantation is considered. We have previously shown that inflammation triggers migration of multi-potential neural precursor cells (NPCs) into the white matter of experimental autoimmune encephalomyelitis (EAE) rodents, a widely used model of MS. Here we investigated the molecular basis of this attraction. NPCs were grown from E13 embryonic mouse brains and transplanted into the lateral cerebral ventricles of EAE mice. Transplanted NPC migration was directed by three tissue-derived chemokines. Stromal cell-derived factor-1α, monocyte chemo-attractant protein-1 and hepatocyte growth factor were expressed in the EAE brain and specifically in microglia and astrocytes. Their cognate receptors, CXCR4, CCR2 or c-Met were constitutively expressed on NPCs. Selective blockage of CXCR4, CCR2 or c-Met partially inhibited NPC migration in EAE brains. Blocking all three receptors had an additive effect and resulted in profound inhibition of NPC migration, as compared to extensive migration of control NPCs. The inflammation-triggered NPC migration into white matter tracts was dependent on a motile NPC phenotype. Specifically, depriving NPCs from epidermal growth factor (EGF) prevented the induction of glial commitment and a motile phenotype (as indicated by an in vitro motility assay), hampering their response to neuroinflammation. In conclusion, signaling via three chemokine systems accounts for most of the inflammation-induced, tissue-derived attraction of transplanted NPCs into white matter tracts during EAE.
Mikhal E Cohen; Nina Fainstein; Iris Lavon; Tamir Ben-Hur
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-6-21
Journal Detail:
Title:  Stem cell research     Volume:  13     ISSN:  1876-7753     ISO Abbreviation:  Stem Cell Res     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-8-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101316957     Medline TA:  Stem Cell Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  227-239     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier B.V.
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