fig1

Figure 1. Schematic overview of MSC priming strategies and EV functional modulation. This diagram illustrates the principal priming strategies applied to MSCs, including hypoxia, inflammatory cytokines, 3D culture systems, oxidative and sulfide compounds, and biomaterials. These stimuli influence the MSC secretory profile, leading to the production of EVs enriched in regulatory microRNAs, proteins and antioxidant enzymes. The molecular reprogramming of EV cargo enhances their therapeutic potential, conferring immunomodulatory, angiogenic, neuroprotective, anti-fibrotic, and antioxidant properties^{[11,12,16,24-26,30-33,51-54,58-62,64-87]}. These features can collectively promote tissue repair and regeneration across diverse disease models. MSC: Mesenchymal stem cell; EV: extracellular vesicle; 3D: three-dimensional; H₂S: hydrogen sulfide; NO: nitric oxide; ECM: extracellular matrix; TGF-β1: transforming growth factor beta 1; ROS: reactive oxygen species; PD-L1: programmed death-ligand 1; miRNA: microRNA; VEGF: vascular endothelial growth factor; HGF: hepatocyte growth factor; FGF: fibroblast growth factor; EGF: epidermal growth factor; ANGPTL4: angiopoietin-like 4; IGFBP3: insulin-like growth factor binding protein 3; EDIL3: EGF-like repeats and discoidin I-like domains 3; IL: interleukin; IDO: indoleamine 2,3-dioxygenase; HLA-G: human leukocyte antigen G; THBS1: thrombospondin 1; BDNF: brain-derived neurotrophic factor; BMP2/7: bone morphogenetic protein 2/7; ENG: endoglin; GRO-α: growth-regulated oncogene alpha; GRO-γ: growth-regulated oncogene gamma; SOD: superoxide dismutase.