Bone marrow mesenchymal stem cell-derived exosomes loaded with miR-26a through the novel immunomodulatory peptide DP7-C can promote osteogenesis

Abstract:Purpose: As small bioactive molecules, exosomes can deliver osteogenesis-related miRNAs to target cells and promote osteogenesis. This study aimed to investigate miR-26a as a therapeutic cargo to be loaded into exosomes through a novel immunomodulatory peptide (DP7-C). In addition, the exosomes secreted from BMSCs were obtained to evaluate their osteogenic capacity. Methods: After transfecting BMSCs with DP7-C as a transfection agent, exosomes were extracted by ultracentrifugation from the culture supernatant of miR-26a-modified BMSCs. Then, we characterized and identified the engineered exosomes. Next, the effect of the engineered exosomes on osteogenesis was evaluated in vitro and in vivo, including in Transwell, wound healing, modified Alizarin red staining, western blot, real-time quantitative PCR, and experimental periodontitis assays. Finally, bioinformatics and data analysis were used to investigate the role of miR-26a in bone regeneration. Results: TheDP7-C/miR-26a complex successfully transfected miR-26a into BMSCs and stimulated them to release a high dosage of exosomes overexpressing miR-26a. Furthermore, exosomes loaded with miR-26a could promote the proliferation, migration, and osteogenic differentiation of BMSCs in vitro and inhibit the destruction of periodontitis in vivo, maintaining the integrity of supporting periodontal tissue. Target gene analysis indicated that the osteogenic effect of miR-26a is related to the mTOR pathway. Conclusion: MiR-26a can be encapsulated into exosomes through DP7-C. Exosomes loaded with miR-26a can promote osteogenesis and inhibit bone loss in experimental periodontitis and serve as the foundation for a novel treatment strategy.