Characterization of extracellular vesicles derived from cortical bone stem cells compared with mesenchymal stem cells

Extracellular vesicles (EVs) are considered useful therapeutic tools in regenerative medicine. They are an alternative to stem cells and drug delivery vehicles, but their properties differ depending on their cell type of origin. Previously, we reported differences in the cellular properties between mouse cortical bone-derived stem cells (mCBSCs) and mouse mesenchymal stem cells (mMSCs). In this study, we aimed to clarify the characteristics of mCBSC-derived EVs (mCBSC-EVs), whose properties remain unclear, and compared them with those of mMSC-EVs. Proteomic analysis identified 3470 proteins in both EVs, of which 224 and 217 were unique to mCBSC-EVs and mMSC-EVs, respectively. Glycomic analysis using lectin microarrays showed significant differences in the relative intensities of various types of lectins between mCBSC-EVs and mMSC-EVs. Specifically, fucosylated glycans, sialic acid structures, and glycans with bisecting N-acetylglucosamine were differentially expressed between mCBSC-EVs and mMSC-EVs. Finally, we examined the uptake and functional effects of EVs on mouse endothelial cells (mECs). mECs preferentially took up mCBSC-EVs than mMSC-EVs. Moreover, mCBSC-EVs resulted in greater upregulation of adhesion and inflammatory molecules in response to TNF-α stimulation than did mMSC-EVs. Furthermore, both mCBSC-EVs and mMSC-EVs elicited comparable levels of tube-like structure formation by mECs. Taken together, our results revealed that mCBSC-EVs and mMSC-EVs exhibit differences in cargo contents and biological action, suggesting the predominance of mCBSC-EVs. Therefore, CBSC-EVs may be useful for treating various physiological and pathological conditions, including wound healing and angiogenesis in ischemic diseases.