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

World Journal of Stem Cells 2022年第7期14卷 453-472页

作者： Victoria Pulido-Escribano bárbara torrecillas-baena Marta Camacho-Cardenosa Gabriel Dorado MaríaÁngeles Gálvez-Moreno Antonio Casado-Díaz Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17 Instituto Maimónides de Investigación Biomédica de CórdobaHospital Universitario Reina SofíaCórdoba 14004Spain Dep.bioquímica y biología Molecular Campus Rabanales C6-1-E17Campus de Excelencia Internacional Agroalimentario(ceiA3)Universidad de CórdobaCIBERFESCórdoba 14071Spain

The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their *** properties include high expansion and differentiation in vitro,low immunogenicity,and modulation of biological processes,such as inflammation,angiogenesis and ***,the regenerative effect of MSC is partly due to their paracrine *** 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 ***,contents of EV can be modulated by preconditioning MSC under different culture *** them,exposure to hypoxia stands out;these cells respond by activating hypoxia-inducible factor(HIF)at low O_(2) *** 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 *** of these genes is reflected in the contents of secreted ***,numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under *** this review,we show the implications of hypoxia responses in relation to tissue *** 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

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Effects of normobaric cyclic hypoxia exposure on mesenchymal stem-cell differentiation–pilot study on bone parameters in elderly

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World Journal of Stem Cells 2020年第12期12卷 1667-1690页

作者： Marta Camacho-Cardenosa JoséManuel Quesada-Gómez Alba Camacho-Cardenosa Alejo Leal GabrielDorado bárbara torrecillas-baena Antonio Casado-Díaz Facultad Ciencias del Deporte Universidad De ExtremaduraCáceres 10003Spain CIbER De Fragilidad Y Envejecimiento Saludable(CIbERFES) Unidad De Gestión Clínica De Endocrinología Y NutriciónInstituto Maimónides De Investigación Biomédica De CórdobaHospital Universitario Reina SofíaCórdoba 14004Spain Servicio de Traumatología Hospital de CáceresCáceres 10004Spain Departamento bioquímica y biología Molecular Campus Rabanales C6-1-E17Campus de Excelencia Internacional Agroalimentario(ceiA3)Universidad de Córdoba-CIBERFES14071 CórdobaSpain

bACKGROUND Mesenchymal stem cells(MSC)of bone marrow are the progenitor of osteoblasts and *** tend to differentiate into adipocytes,instead of osteoblasts,with *** favors the loss of bone mass and development of *** induces hypoxia inducible factor 1αgene encoding transcription factor,which regulates the expression of genes related to energy metabolism and *** allows a better adaptation to low O2 *** hypoxia has negative effects on bone metabolism,favoring bone ***,surprisingly,cyclic hypoxia(CH),short times of hypoxia followed by long times in normoxia,can modulate MSC differentiation and improve bone health in *** To evaluate the CH effect on MSC differentiation,and whether it improves bone mineral density in *** MSC cultures were induced to differentiate into osteoblasts or adipocytes,in CH(3%O2 for 1,2 or 4 h,4 d a week).Extracellular-matrix mineralization and lipid-droplet formation were studied in MSC induced to differentiate into osteoblast or adipocytes,*** addition,gene expression of marker genes,for osteogenesis or adipogenesis,have been quantified by quantitative real time polymerase chain *** in vivo studies with elderly(>75 years old;n=10)were carried out in a hypoxia chamber,simulating an altitude of 2500 m above sea level,or in normoxia,for 18 wk(36 CH sessions of 16 min each).Percentages of fat mass and bone mineral density from whole body,trunk and right proximal femur(femoral,femoral neck and trochanter)were assessed,using dual-energy X-ray *** CH(4 h of hypoxic exposure)inhibited extracellular matrix mineralization and lipid-droplet formation in MSC induced to differentiate into osteoblasts or adipocytes,***,both parameters were not significantly affected by the other shorter hypoxia times *** longest periods of hypoxia downregulated the expression of genes related to extracellular matrix

关键词： Normobaric cyclic hypoxia Mesenchymal stem cells Cellular differentiation Osteoblasts Adipocytes bone health

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