Tailored apoptotic vesicles promote bone regeneration by stepping on osteoinductive accelerator via ITGA10-AKT signaling activation

Apoptotic vesicles (apoVs) have shown good potential in treating bone disease including osteoporosis. However, the efficient production of highly energetic apoVs is one of the critical limitations for their clinical applications. In this study, we contributed to reconstructing a gradual senescence process in mesenchymal stem cell (MSC)-derived apoVs. Our findings displayed that their essential properties remained consistent throughout replicative aging and individual’s aging. Nevertheless, their protein composition and biological functions were significantly altered by the age of donor. Through proteomic assay, we identified integrin α 10 (ITGA10) as a highly efficient apoV osteoinductivity accelerator in both humans and mice, and have targeted it for apoV customization. On this basis, we demonstrated accelerator-based approaches to prepare amounts of ITGA10-enriched apoVs by magnetic-activated sorting and sonic loading. These engineered apoVs proved effective in ameliorating osteoprotic bone loss. Their osteoinductivity was attributed to the activation of downstream AKT signaling in recipient MSCs by the high content of ITGA10. In summary, we have laid the groundwork for customizing apoVs through an accelerator-based strategy, aiming to obtain superior therapeutic effectors in the field of bone regenerative biomedicine.