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-modi ed BMSCs. Then, we characterized and identi ed the engineered exosomes. Next, the effect of the engineered exosomes on osteogenesis was evaluated in vitro and in vivo, including in Transwell, wound healing, modi ed 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: The DP7-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.

Injectable Hydrogel To Deliver Bone Mesenchymal Stem Cells Preloaded with Azithromycin To Promote Spinal Cord Repair

“…We attribute these therapeutic effects of complete hydrogel to the anti-inflammatory activity not only of azithromycin but also of BMSCs, which can dampen immune responses to spinal cord injury and mitigate the associated inflammatory damage. , In addition, BMSCs can differentiate into target cell types at the site of injury, promoting tissue repair and restoring tissue integrity. After BMSCs encapsulated TAT-AZM-NPs to form BMSCs-TAT-AZM-NPs, they enhanced the stability and sustained release of the drug delivery system, thereby enhancing the therapeutic efficacy.…”

“…We attribute these therapeutic effects of complete hydrogel to the anti-inflammatory activity not only of azithromycin but also of BMSCs, which can dampen immune responses to spinal cord injury and mitigate the associated inflammatory damage. 43,44 In addition, BMSCs can differentiate into target cell types at the site…”

Small Extracellular Vesicles Laden Oxygen-Releasing Thermosensitive Hydrogel for Enhanced Antibacterial Therapy against Anaerobe-Induced Periodontitis Alveolar Bone Defect

“…Similar to the activity of stem cells, MSCs-derived sEVs have been shown to reduce periodontal inflammation and enhance soft and hard tissue regeneration by regulating the expression of inflammation-related proteins and a range of signaling processes . Currently, several studies have reported that MSCs-derived sEVs can mediate periodontal inflammation by promoting periodontal cell proliferation and migration and down-regulating the expression level of apoptosis-related cytokines and form functional periodontal fibers that span the tooth root surface and new bone. − In particular, BMMSCs-derived sEVs could regulate inflammatory response by influencing the polarization of macrophages through bone metabolism, prevent the development of periodontitis and the signaling pathways related to immune damage of periodontal tissue caused by inflammation, and then deliver osteogenesis-related miRNAs to target cells for improving the bone loss caused by periodontitis and promoting bone formation . Thus, loading BMMSCs-sEVs into the hydrogels described above can achieve the rapid repair of the periodontal tissue.…”

“…25−27 In particular, BMMSCs-derived sEVs could regulate inflammatory response by influencing the polarization of macrophages through bone metabolism, prevent the development of periodontitis and the signaling pathways related to immune damage of periodontal tissue caused by inflammation, and then deliver osteogenesis-related miRNAs to target cells for improving the bone loss caused by periodontitis and promoting bone formation. 61 Thus, loading BMMSCs-sEVs into the hydrogels described above can achieve the rapid repair of the periodontal tissue. Here, we successfully combined BMMSCs-sEVs with a thermosensitive antibacterial hydrogel loaded with oxygen-releasing particles benefiting from their antibiosis properties, thus synergistically promoting wound healing and restoring the complete structure and function of alveolar bone defects in periodontitis rats.…”

Emerging roles of exosomes in oral diseases progression

“…These functional modifications significantly improve bone regeneration through the exosomes, targeting the BMP2-associated signaling cascade/mTOR pathway. 199 , 200 Moreover, immune modifications performed by engineered exosomes also promote bone regeneration. Dendritic cell-derived exosomes loaded with IL-10 and TGF-β can inhibit immune-related bone resorption and suppress bone loss.…”