Thursday, 7 August 2014

How do you get neural cells around the brain

Cohen ME, Fainstein N, Lavon I, Ben-Hur T. Signaling through three chemokine receptors triggers the migration of transplanted neural precursor cells in a model of multiple sclerosis. Stem Cell Res. 2014;13(2):227-239.

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 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.

When you get inflammation you get tissue damage and then after that you get tissue repair, because the function of such a response has evolved to get rid of infections and then repair the damage. Part of the repair process can be getting neural stem cells into the sites of damage to bring about repair. They migrate in response to chemical signals and some of these proteins are called chemokines
This study shows that they use three in particular

Stromal cell-derived factor-1α,CXCL12
CXCL12 is strongly chemotactic for lymphocytes. In adulthood, CXCL12 plays an important role in blood vessel formation by recruiting endothelial progenitor cells (EPCs) from the bone marrow through a CXCR4 dependent mechanism.
monocyte chemo-attractant protein-1 CCL2CCL2 exhibits a chemotactic activity for monocytes and basophils.
hepatocyte growth factor is a cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts on haemopoietic progenitor cells. It has been shown to have a major role in embryonic organ development, in adult organ regeneration and in wound healing

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