Many degenerative diseases of the central nervous system (CNS) are associated with demyelination. Oligodendrocyte precursor cells (OPCs) are potential stem cells that can differentiate into oligodendrocytes (OLs) and promote myelination. Promoting the proliferation of OPCs is key to stimulating remyelination and treating neurodegenerative diseases. Herein, we report that astrocytes (ASTs) could increase exosomal secretion of OPCs to promote their proliferation via ITGB4-mediated cell adhesion. Our results demonstrate that ASTs can regulate the proliferation of OPCs through ITGB4-mediated exosomal secretion. OPC proliferation is significantly increased after direct-contact culture with ASTs. Gene ontology (GO) and KEGG pathway analyses reveal that ITGB4/extracellular exosome are closely related to OPC proliferation. siRNA ITGB4 decreases exosomal secretion and OPC proliferation. ITGB4/exosomes remarkably promote OPC transition from G1 to S phase. Furthermore, exosomes can alleviate the inhibitory effect of ITGB4 knockdown on OPC proliferation. Collectively, ASTs regulate OPC exosomal secretion via ITGB4, which could be a valuable approach for promoting OPC proliferation. This strategy may represent a potential treatment for neurological diseases caused by demyelination. (C) 2020 Elsevier Inc. All rights reserved.