Exosomes derived from mesenchymal stromal cells promote bone regeneration by delivering miR-182–5p-inhibitor

• Published in: Pharmacological research Vol. 192; p. 106798
• Main Authors: Zhu, Qinghai, Tang, Yuting, Zhou, Tian, Yang, Li, Zhang, Gao, Meng, Ying, Zhang, Huixin, Gao, Jun, Wang, Chenxing, Su, Yu-Xiong, Ye, Jinhai
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.06.2023; Elsevier
• Subjects: BMSC; Bone regeneration; Bone Regeneration - genetics; Cell Differentiation; Exosomes; Exosomes - genetics; Exosomes - metabolism; Humans; Mesenchymal Stem Cells - metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; MiRNA; Osteogenesis; Phosphatidylinositol 3-Kinases - metabolism; Scaffold; Tissue engineering; ARS; BMSC; Col1α; Bone regeneration; Tissue engineering; ALP; MiRNA; Scaffold; Exosomes; OPN; RUNX2; MSCs; AB-BMSCs; PLLA; BMD; OCN; Exo; RT-qPCR; BMSCs
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2023.106798

Exosomes, small extracellular vesicles that function as a key regulator of cell-to-cell communication, are emerging as a promising candidate for bone regeneration. Here, we aimed to investigate the effect of exosomes from pre-differentiated human alveolar bone-derived bone marrow mesenchymal stromal cells (AB-BMSCs) carrying specific microRNAs on bone regeneration. Exosomes secreted from AB-BMSCs pre-differentiated for 0 and 7 days were cocultured with BMSCs in vitro to investigate their effect on the differentiation of the BMSCs. MiRNAs from AB-BMSCs at different stages of osteogenic differentiation were analyzed. BMSCs seeded on poly-L-lactic acid(PLLA) scaffolds were treated with miRNA antagonist-decorated exosomes to verify their effect on new bone regeneration. Exosomes pre-differentiated for 7 days effectively promoted the differentiation of BMSCs. Bioinformatic analysis revealed that miRNAs within the exosomes were differentially expressed, including the upregulation of osteogenic miRNAs (miR-3182, miR-1468) and downregulation of anti-osteogenic miRNAs (miR-182–5p, miR-335–3p, miR-382–5p), causing activation of the PI3K/Akt signaling pathway. The treatment of BMSC-seeded scaffolds with anti-miR-182–5p decorated exosomes demonstrated enhanced osteogenic differentiation and efficient formation of new bone. In conclusion, Osteogenic exosomes secreted from pre-differentiated AB-BMSCs were identified and the gene modification of exosomes provides great potential as a bone regeneration strategy. Data generated or analyzed in this paper partly are available in the GEO public data repository(http://www.ncbi.nlm.nih.gov/geo). [Display omitted]