Work

Mesenchymal stromal cell-derived small extracellular vesicles modulate macrophage polarization and enhance angio-osteogenesis to promote bone healing

Year: 2021

Type: article

Abstract: Mesenchymal stromal cell-derived small extracellular vesicles modulate macrophage polarization and enhance angio-osteogenesis to promote bone healingMesenchymal stem/stromal cells (MSCs) have demonstrated therapeutic efficacy for bone regeneration in animal and clinical studies.Although MSCs were initially thought to differentiate to various cell types to replace the injured/ diseased tissue, it is now accepted that these cells secrete factors to promote tissue repair. 1 Among these factors, small extracellular vesicles (sEVs) of size 50e200 nm, which include the exosomes, have been identified as the principal agent mediating the wide-ranging therapeutic efficacy of MSCs. 2 Several studies have also reported the therapeutic effects of MSC-sEVs to enhance bone repair in animal models, as recently reviewed.3 However, the cellular processes and mechanisms mediated by MSC-sEVs in bone regeneration remain to be fully elucidated.In this study, we employed a rat calvaria defect model to investigate the cellular processes activated by MSC-sEVs during bone repair (Supplementary Methods).Briefly, MSC-sEVs were prepared as previously described, 4 and characterized in accordance with the MISEV2018 guidelines.5 Collagen sponges with 100 mg MSC-sEVs in 100 ml PBS (CS/ sEVs) or equivalent volume of phosphate-buffered saline (PBS, CS/Control) were implanted to 8-mm diameter critical-size calvaria defects surgically created in 32 rats.Another five rats served as age-matched naive control.At 1 and 8 weeks, samples were harvested for analyses using micro-computed tomography (micro-CT), histology and immunohistochemistry.Micro-CT analysis revealed minimal bone formation in both groups at 1 week (Fig. S1).Despite limited bone formation, CS/sEVs group showed better cell infiltration and Peer review under responsibility of Chongqing Medical University.

Source: Genes & Diseases

DOI: 10.1016/j.gendis.2021.11.012