title: Hyperglycemia Induces Bioenergetic Changes in Adipose-Derived Stromal Cells While Their Pericytic Function Is Retained.
abstract: Diabetic retinopathy (DR) is a hyperglycemia (HG)-mediated microvascular complication. In DR, the loss of pericytes and subsequently endothelial cells leads to pathologic angiogenesis in retina. Adipose-derived stromal cells (ASC) are a promising source of therapeutic cells to replace lost pericytes in DR. To date, knowledge of the influence of HG on the bioenergetics and pericytic function of ASC is negligible. Human ASC were cultured in normoglycemia medium (5 mM d-glucose) or under HG (30 mM d-glucose) and assessed. Our data showed that HG increased the level of apoptosis and reactive oxygen species production in ASC, yet their proliferation rate was not affected. HG induced alterations in mitochondrial function and morphology in ASC. HG also strongly affected the bioenergetic status of ASC in which both the maximum oxygen consumption rate and extracellular acidification rate were decreased. This was corroborated by a reduced uptake of glucose under HG. In spite of these observations, in vitro, ASC promoted the formation of vascular-like networks of human umbilical vein endothelial cells on monolayers of ASC under HG with minimally affected.
authors.affiliation: 1 Department of Pathology and Medical Biology, University Medical Center Groningen , University of Groningen, Groningen, the Netherlands .
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Hajmousa
authors.affiliation: 2 Millennium Institute of Immunology and Immunotherapy , Santiago, Chile .|3 Faculty of Biological Sciences and Faculty of Medicine, Center for Biomedical Research , Universidad Andres Bello, Santiago, Chile .
authors.forename: Alvaro A
authors.initials: AA
authors.lastname: Elorza
authors.affiliation: 4 Department of Pediatrics and Laboratory Medicine, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen , Groningen, the Netherlands .
authors.forename: Vera J M
authors.initials: VJ
authors.lastname: Nies
authors.affiliation: 3 Faculty of Biological Sciences and Faculty of Medicine, Center for Biomedical Research , Universidad Andres Bello, Santiago, Chile .
authors.forename: Erik L
authors.initials: EL
authors.lastname: Jensen
authors.affiliation: 1 Department of Pathology and Medical Biology, University Medical Center Groningen , University of Groningen, Groningen, the Netherlands .
authors.forename: Ruxandra A
authors.initials: RA
authors.lastname: Nagy
authors.affiliation: 1 Department of Pathology and Medical Biology, University Medical Center Groningen , University of Groningen, Groningen, the Netherlands .
authors.forename: Martin C
authors.initials: MC
authors.lastname: Harmsen
mesh_terms: D000143:Acids / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D005947:Glucose / Q000633:toxicity; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism* / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D000143:Acids; D017382:Reactive Oxygen Species; D005947:Glucose