Premium
Mesenchymal stem cells instruct a beneficial phenotype in reactive astrocytes
Author(s) -
Vigo Tiziana,
VoulgariKokota Androniki,
Errede Mariella,
Girolamo Francesco,
Ortolan Jasmin,
Mariani Maria C.,
Ferrara Giovanni,
Virgintino Daniela,
Buffo Annalisa,
Kerlero de Rosbo Nicole,
Uccelli Antonio
Publication year - 2021
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23958
Subject(s) - astrogliosis , mesenchymal stem cell , astrocyte , experimental autoimmune encephalomyelitis , biology , remyelination , stem cell , immunology , neurodegeneration , neural stem cell , progenitor cell , glial scar , multiple sclerosis , microbiology and biotechnology , pathology , neuroscience , medicine , central nervous system , myelin , disease
Abstract Transplanted mesenchymal stromal/stem cells (MSC) ameliorate the clinical course of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), reducing inflammation and demyelination. These effects are mediated by instructive cross‐talk between MSC and immune and neural cells. Astroglial reaction to injury is a prominent feature of both EAE and MS. Astrocytes constitute a relevant target to control disease onset and progression and, based on their potential to acquire stem cell properties in situ, to foster recovery in the post‐acute phase of pathology. We have assessed how MSC impact astrocytes in vitro and ex vivo in EAE. Expression of astroglial factors implicated in EAE pathogenesis was quantified by real‐time PCR in astrocytes co‐cultured with MSC or isolated from EAE cerebral cortex; astrocyte morphology and expression of activation markers were analyzed by confocal microscopy. The acquisition of neural stem cell properties by astrocytes was evaluated by neurosphere assay. Our study shows that MSC prevented astrogliosis, reduced mRNA expression of inflammatory cytokines that sustain immune cell infiltration in EAE, as well as protein expression of endothelin‐1, an astrocyte‐derived factor that inhibits remyelination and contributes to neurodegeneration and disease progression in MS. Moreover, our data reveal that MSC promoted the acquisition of progenitor traits by astrocytes. These data indicate that MSC attenuate detrimental features of reactive astroglia and, based on the reacquisition of stem cell properties, also suggest that astrocytes may be empowered in their protective and reparative actions by MSC.