title: Opposite Effects of Mechanical Action of Fluid Flow on Proangiogenic Factor Secretion From Human Adipose-Derived Stem Cells With and Without Oxidative Stress.
abstract: Mechanical forces, hypoxia, and oxidative stress contribute to skin renewal, perfusion, and wound healing, but how are they regulating subcutaneous adipose-derived stem cells (ASCs) in the inflammatory microenvironment associated to skin repair and disorders is unknown. In this study, ASCs were isolated from lipoaspirate samples from plastic surgery patients, primary cultured and their differentiation and secretion of a panel of cytokines with pronounced effects on skin repair and angiogenesis were studied under mechanical stimulation by intermittent fluid flow, 1% hypoxia and oxidative stress by glutathione (GSH) depletion with buthionine sulfoximine (BSO) treatment. Mechanical action of fluid flow did not alter mesenchymal phenotype of CD90+/CD29+/CD44+/CD34-/CD106-/CD45-ASCs; however, it remarkably induced ASC secretion of human umbilical vein endothelial cell (HUVEC) migration-stimulating factors. Multiplex Luminex assay further confirmed an increased secretion of VEGF, G-CSF, HGF, Leptin, IL-8, PDGF-BB, Angiopoietin-2, and Follistatin from mechanically-stimulated ASCs via cyclooxygenase-2. Consistent with this mechanism, GSH depletion and hypoxia also increased ASC secretion of VEGF, IL-8, leptin, Angiopoitein-2, and PDGF-BB. However, mechanical action of fluid flow abrogated VEGF and HUVEC migration-stimulating activity from GSH-depleted and hypoxic ASCs. Conversely, GSH depletion and hypoxia abrogated VEGF and HUVEC migration-stimulating activity from mechano-stimulated ASCs. Although mechanical action of fluid flow, hypoxia, and GSH-depletion had independent proangiogenic-stimulating activity on ASCs, mechanical stimulation had opposite effects on proangiogenic factor secretion from ASCs with and without oxidative stress. These data uncover the role of hypoxia and endogenous redox balance during the proangiogenic response of ASCs and other mesenchymal-derived cell types to mechanical action of interstitial fluid flow. J. Cell. Physiol. 232: 2158-2167, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Institute of Applied Molecular Medicine (IMMA), CEU-San Pablo University School of Medicine, Boadilla del Monte, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bravo
authors.affiliation: Institute of Applied Molecular Medicine (IMMA), CEU-San Pablo University School of Medicine, Boadilla del Monte, Madrid, Spain.
authors.forename: Cira
authors.initials: C
authors.lastname: García de Durango
authors.affiliation: Department of Molecular and Cellular Oncology Houston, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: González
authors.affiliation: Institute of Applied Molecular Medicine (IMMA), CEU-San Pablo University School of Medicine, Boadilla del Monte, Madrid, Spain.
authors.forename: Arancha R
authors.initials: AR
authors.lastname: Gortázar
authors.affiliation: Institute of Applied Molecular Medicine (IMMA), CEU-San Pablo University School of Medicine, Boadilla del Monte, Madrid, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Santos
authors.affiliation: Valencia Institute of Pathology (IVP), Catholic University of Valencia School of Medicine and Odontology, Valencia, Spain.
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Forteza-Vila
authors.affiliation: Valencia Institute of Pathology (IVP), Catholic University of Valencia School of Medicine and Odontology, Valencia, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Vidal-Vanaclocha
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D042501:Angiogenic Proteins / Q000378:metabolism*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D015687:Cell Hypoxia; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D002633:Chemotaxis; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000172:deficiency; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D019899:Paracrine Communication; D010641:Phenotype; D061251:Primary Cell Culture; D055153:Stem Cell Niche; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D042501:Angiogenic Proteins; D017077:Culture Media, Conditioned; D016207:Cytokines; D019328:Buthionine Sulfoximine; D005978:Glutathione