Epub: Piao et al. CD44 is required for the migration of transplanted oligodendrocyte progenitor cells to focal inflammatory demyelinating lesions in the spinal cord. Glia. 2012. doi: 10.1002/glia.22438.
Remyelination of chronically demyelinated axons in multiple sclerosis (MS) requires the recruitment of endogenous cells or their replacement by transplanted, exogenous oligodendrocyte progenitor cells (OPCs). We have previously shown that an OPC line, CG4, preferentially migrates after transplantation toward focal areas of inflammatory demyelination and axon loss created by injection of zymosan in the rat spinal cord. Here we show that many transplanted CG4 cells had already migrated into the inflammatory lesion after 1 day. We demonstrate that a large number of CG4 cells that had migrated, expressed the adhesion protein, CD44, and that CD44's main ligand, hyaluronic acid (HA) was robustly expressed in the inflammatory lesion. In an in vitro migration assay, migration declined significantly following blocking of CD44 expression on CG4 cells. Likewise, migration of CG4 cells toward a zymosan lesion in vivo was inhibited when transplanted cells were exposed to a CD44 blocking antibody prior to transplantation. These findings suggest that CD44 is a key molecule in the migration of OPCs toward the focal inflammatory demyelinated lesion induced by zymosan, and may be an important in OPC repair in MS.
CD44 is an adhesion molecule used by cells to be recruited into the CNS. This molecule is also used by effector white blood cells to get into the CNS as we showed years ago. Likewise others have shown that CD49d is also used by white blood cells and neural stem cells to migrate into lesions, although in rodents at least CD44 blockade is much more effective at inhibiting disease than blockage with CD49d (The target for tysabri). But shows that biology can use the same pathways so whilst blockade of white cells into the brain may be good it could be at a cost of blocking repairing cells entering also. This will only be of relevance for transplanting of oligodendrocyte precursors because in reality it is not they that migrate into the CNS but there neural stem cell precursors.