Mesenchymal stem cells instruct a beneficial phenotype in reactive astrocytes

AbstractTransplanted mesenchymal stromal/stem cells (MSC) ameliorate the clinical course ofexperimental autoimmune encephalomyelitis (EAE), a mouse model of multiple scle-rosis (MS), reducing inflammation and demyelination. These effects are mediated byinstructive cross-talk between MSC and immune and neural cells. Astroglial reactionto injury is a prominent feature of both EAE and MS. Astrocytes constitute a relevanttarget to control disease onset and progression and, based on their potential toacquire stem cell properties in situ, to foster recovery in the post-acute phase ofpathology. We have assessed how MSC impact astrocytes in vitro and ex vivo inEAE. Expression of astroglial factors implicated in EAE pathogenesis was quantifiedby real-time PCR in astrocytes co-cultured with MSC or isolated from EAE cerebralcortex; astrocyte morphology and expression of activation markers were analyzed byconfocal microscopy. The acquisition of neural stem cell properties by astrocytes wasevaluated by neurosphere assay. Our study shows that MSC prevented astrogliosis,reduced mRNA expression of inflammatory cytokines that sustain immune cell infil-tration in EAE, as well as protein expression of endothelin-1, an astrocyte-derivedfactor that inhibits remyelination and contributes to neurodegeneration and diseaseprogression in MS. Moreover, our data reveal that MSC promoted the acquisition ofprogenitor traits by astrocytes. These data indicate that MSC attenuate detrimentalfeatures of reactive astroglia and, based on the reacquisition of stem cell properties,also suggest that astrocytes may be empowered in their protective and reparativeactions by MS