Bioinspired artificial nanovesicles engineered from 3D spheroid-cultured UC-MSCs enhance angiogenic activity in vitro: functional proof-of-concept for ischemic applications

Artificial nanovesicles (aNVs) derived from cells may mimic naturally secreted extracellular vesicles (EVs) and are becoming popular in biomedical research. We isolated aNVs from two-dimensional (2D)- and three-dimensional (3D)-cultured umbilical cord-derived mesenchymal stem cells (UC-MSCs) (aNVs^2D and aNVs^3D, respectively) and characterized them using Western blotting and electron microscopy. The aNVs^3D showed higher expression of IL-6 and SDF-1α than aNVs^2D. <i>In vitro</i> treatment with aNVs^2D and aNVs^3D resulted in their internalization into endothelial cells and the subsequent alteration of endothelial cell proliferation, migration, and tube formation. Both aNVs were positive for EVs and cell markers and were round in shape. Furthermore, aNVs^3D treatment enhanced endothelial cell proliferation, migration, and tube formation more effectively than aNVs^2D treatment. Our study demonstrates that aNVs3D are potent inducers of angiogenesis, indicating their potential in cell-free ischemia treatment.