Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles  

作　　者：Victoria Pulido-Escribano Bárbara Torrecillas-Baena Marta Camacho-Cardenosa Gabriel Dorado MaríaÁngeles Gálvez-Moreno Antonio Casado-Díaz 

机构地区：[1]Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17,Instituto Maimónides de Investigación Biomédica de Córdoba,Hospital Universitario Reina Sofía,Córdoba 14004,Spain [2]Dep.Bioquímica y Biología Molecular,Campus Rabanales C6-1-E17,Campus de Excelencia Internacional Agroalimentario(ceiA3),Universidad de Córdoba,CIBERFES,Córdoba 14071,Spain

出　　处：《World Journal of Stem Cells》2022年第7期453-472,共20页世界干细胞杂志（英文版）（电子版）

基　　金：Supported by “Instituto de Salud Carlos III”(ISCIII);“Ministerio de Economía y Competitividad”(MINECO) and European Union (EU),No. PI18/01659 and No. PI21/01935

摘　　要：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 O_(2) 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.

关 键 词：Cell priming Extracellular vesicles HYPOXIA Hypoxia-inducible factor Mesenchymal stemcells Regenerative medicine 

分 类 号：R457.7[医药卫生—治疗学]