RT Journal Article T1 Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles. A1 Pulido-Escribano, Victoria A1 Torrecillas-Baena, Barbara A1 Camacho-Cardenosa, Marta A1 Dorado, Gabriel A1 Galvez-Moreno, Maria Angeles A1 Casado-Diaz, Antonio K1 Cell priming K1 Extracellular vesicles K1 Hypoxia K1 Hypoxia-inducible factor K1 Mesenchymal stem-cells K1 Regenerative medicine AB The use of mesenchymal stem-cells (MSC) in cell therapy has received considerable attention because of their properties. These properties include high expansion and differentiation in vitro, low immunogenicity, and modulation of biological processes, such as inflammation, angiogenesis and hematopoiesis. Curiously, the regenerative effect of MSC is partly due to their paracrine activity. This has prompted numerous studies, to investigate the therapeutic potential of their secretome in general, and specifically their extracellular vesicles (EV). The latter contain proteins, lipids, nucleic acids, and other metabolites, which can cause physiological changes when released into recipient cells. Interestingly, contents of EV can be modulated by preconditioning MSC under different culture conditions. Among them, exposure to hypoxia stands out; these cells respond by activating hypoxia-inducible factor (HIF) at low O2 concentrations. HIF has direct and indirect pleiotropic effects, modulating expression of hundreds of genes involved in processes such as inflammation, migration, proliferation, differentiation, angiogenesis, metabolism, and cell apoptosis. Expression of these genes is reflected in the contents of secreted EV. Interestingly, numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under normoxia. In this review, we show the implications of hypoxia responses in relation to tissue regeneration. In addition, hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV, with a high potential for clinical use in regenerative medicine that can be applied to different pathologies. PB Baishideng Publishing Group SN 1948-0210 YR 2022 FD 2022-07-11 LK http://hdl.handle.net/10668/21633 UL http://hdl.handle.net/10668/21633 LA en NO Pulido-Escribano V, Torrecillas-Baena B, Camacho-Cardenosa M, Dorado G, Gálvez-Moreno MÁ, Casado-Díaz A. Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles. World J Stem Cells. 2022 Jul 26;14(7):453-472 DS RISalud RD Apr 18, 2025